3 Bromopyruvate

Other names: 3BP, 3-Bromopyruvic Acid
CAS number:1113-59-3

Source:

The info shared here came from multiple directions. That includes literature research, personal experience, a lot of ideas discussed and shared on Cancer Compass, discussion with a good number of professors and doctors, discussion with German clinics, discussions with patients.

My opinion:

For an update on my opinion related to 3BP please check the following post too: http://www.cancertreatmentsresearch.com/?p=725

I went through ups and downs with my opinion regarding 3BP anti-cancer effectiveness. But today, based on what I saw, based on the science behind, based on input from various doctors and clinics around the world using 3BP, and input from many patients, I believe 3BP has serious anti cancer potential. BUT, what I also learn more and more is that it has its challenges too. It is challenging to administer 3BP so that we get the best outcome. However, based on all the input I mention above, I think we are on the right track to identifying the right administration protocol.

The administration protocol can make the difference between failure and success. As a result, some doctors/clinics will stopped using 3BP because of very limited or even negative results and others are getting great results.

If 3BP is not used as a part of correct treatment protocol (e.g. including other glycolisis inhibitors and/or angiogenesis inhibitors), in some cases, according to a few US doctors, the 3BP treatment may lead first to a decline of tumor size and after that to a faster growth in the same way as chemo does in some cases. I believe this is because 3BP may kill the outside layer of tumor related to cells sensitive to 3BP (via MCT1 transporters), exposing the patient to highly glycolitic cells not sensitive to 3BP. If this view is true, in the next treatment step the highly glycolitic cells may potentially be killed by e.g. 2DG or high dose Vitamin C or their growth may be inhibited by angiogenesis inhibitors.

Here is the treatment protocol I currently believe can address some of the potential issues suggested above: http://www.cancertreatmentsresearch.com/?p=184

Warning: During the summer of 2016, a clinic in Germany using 3BP IV had an unfortunate experience, seeing three of its patients death in a short time frame of a few to several days. One of the treatments used for their patients was 3BP, next to others such as Vitamin C, etc. 3BP was suspected to cause the death of the patients (Ref.). However, it is difficult to understand how 3BP would have triggered such a result given that the clinic was using 3BP for more than a year to treat its patients. The case is currently under investigations. Association of this unfortunate event with 3BP is also difficult to understand since multiple clinics and patients around the world used 3BP for long time frames, even longer than one year, without reporting any side effects. Nevertheless, this event should make us realize that stage IV cancer treatments, whether conventional or not, represent a step in uncharted territory where the risks are little known or totally unknown.

Summary

The anti-cancer potential of 3BP has been demonstrated by Dr. Ko while working in the lab of Prof. Pedersen at Johns Hopkins University sometime around 2002. Here is a link to Prof. Pedersen’s lab. Dr. Geschwind who at that time was working at Johns Hopkins University as well, publish his own patents in addition to those of Dr. Ko. As a result, there were two groups of researchers claiming the rights and both created their own company.

As a side note, I did have a few e-mail conversations with Prof. Pedersen and I appreciate his great honesty. I am also very  impressed to see how he is always giving the whole credit to Dr. Ko for the discovery (while to my knowledge, most in the academic world would not do the same). Here is a comprehensive presentation of prof. Pedersen at the NCI and NIH in Unated States. Interestingly, Prof. Pedersen sent a personal letter to President Obama about this matter on January 22, 2013. The president’s mother died of ovarian cancer at the early age of 53. Months later, Prof. Pedersen had still received no response from the president. (Ref.)

Regarding the two main companies associated with the patents on 3BP, that of Dr. Ko is not very visible. However, while not visible, I think Dr. Ko is conducting clinical trials by supporting some doctors, mostly outside of the US, with both the administration protocol and the formulated 3BP. Dr. Ko’s company is called KoDiscovery and is located in Baltimore,  Maryland, United States. What is also clear is that she was the one who supported the first known application of 3BP in humans which also had great success (see case report below). Dr. Geschwind, on the other hand, has gained FDA approval with his company Presciencelabs intending to soon start clinical trials (this was stated in 2013 and three years latter there is still no trial). The patent battle seems to be the reason why things are moving so slowly.

Here are recent news (Nov 2015) related to the legal discussions between the inventors: http://holmansbiotechipblog.blogspot.ca/2015/11/court-dismisses-disaffected-professors.html

There are so many points to discuss about this substance but here are the most relevant points in my view:
– this is a substance with good potential against cancer
– it has clear science behind it and there is a lot of academic research supporting its potential
– it has been used on animals with great success
– it has been used on humans with success (both published and unpublished reports used with effectiveness on: liver cancer, melanoma, lung cancer, adrenal cancer, breast cancer, pancreatic cancer, prostate cancer, etc.)
– it is a very low cost substance
– it can be easily accessed
– it is water soluble so that it can be administered via IV, orally, topically, via nebulizer, or enema
– it is relevant for most types of cancers: it is a metabolic treatment (inhibiting energy production in cancer) and not genetic – this means that the response is not dependent on the very complex genetic profile
– a requirement is that the cancer is visible on PET – however there is no certainty that all cancers visible on PET will respond. In addition to the PET visibility, it needs to have an expression of the MCT1 transporters (see below under Mechanism)
– it is toxic to cancer cells and non-toxic to normal cells through MCT1 selectivity (it is non toxic at the right dose which is discussed below)

Some of the main challenges related to this substance are that its stability is very limited, and it is an acidic substance. The stability declines when temperature increases and when the pH of the solution in which 3BP is mixed increases. Light will also negatively affect its stability.

When delivering to humans, the acidity has to be reduced, i.e pH of the solution has to be increased, which in turn will reduce its stability. However, there are ways to balance those aspects so that the substance can be administered to humans at an acceptable pH while still being effective. There are several patents addressing that, and Ko’s patent is one of those.

Case reports

1. Dr. Ko provide the 3BP  used for the first time officially on humans, by Prof. Vogl. Specifically, it has been administered to a Dutch boy in 2012 at Frankfurt University in Germany, via a technique called TACE, administrating 3BP locally to the liver. The boy was in a terminal phase (liver cancer) and a few applications of the 3BP via TACE succeeded to kill his cancer. As a result the boy had his life extended. The boy passed away a few years later due to a reason other than cancer. What is extremely important is that the cancer had been eliminated and this was a huge result.  Here is the published case. The intervention was performed by Prof. Vogl.
It is amazing that the treatment had such great success in the context that conventional medicine had nothing to offer and that society did not react to this and push 3BP fast to application on humans. However, there is an entire world that has been developed “underwater” and in this world 3BP is today applied on humans even via TACE.

2. 3BP has been applied on a late-phase melanoma cancer patient, via IV administration, at a hospital in Egypt (read the publication here). The patient did not survive due to extensive lung damage caused by cancer, but importantly, the 3BP succeeded to completely deactivate the cancer. Next to showing the high relevance of 3BP in eradicating cancers relying on glycolysis, this report also shows that the effectiveness of such pro-oxidant strategies can be strongly supported by concomitant depletion of glutathione with common drugs such as paracetamol (acetaminophen in US and Canada). (Note: it is well known that glutathione is one of the main factors leading to resistance of cancer to pro-oxidant therapies, and I am wondering why cancer patients do not typically receive paracetamol specifically administered before the administration of various chemotherapies).

Anecdotal reports/stories

Besides the liver cancer and melanoma cases reported in the literature, here are a few examples of stage IV cases that I am aware of:

prostate cancer: a cancer scientist for 30 years treating his prostate cancer during chemo treatment. Chemo alone had no anti-cancer effect. Adding 3BP + paracetamol (used to reduce glutathione) lead to decline in PSA level. He used oral administration only at 2mg/kg/day (solution at pH 4 to 5). Treatment at home.
breast cancer: a 40 to 50 years old lady with various metastases using a few IVs and intensive oral and topical administration (unknown dosage). She was given a few months to go and after about one to two months treatment many of her tumors were gone. 
– adrenal cancer: one month treatment IV (2x/week) led to a reduction of tumor markers of about 10% and a reduction of tumor of 16% in a month as shown on CT scan.
lung cancer: about one month oral and topical administration leading to eradication of a one cm tumor in the lung and 50% decrease of a lymph note. Treatment at home.
pancreatic cancer: Patient utilized 3BP, IV€™s, an oral protocol, hyperthermia, EWOT, fresh green juices, colonics, etc. This led to serious reduction of the tumor markers. Case reported at Dayspring Clinic
breast cancer: another patient treated and reported at Dayspring Clinic
– lung cancer – extensive stage small cell lung cancer (ES-SCLC): 3BP + Salinomycin treatment during about one month leading to complete disappearance of SCLC as shown on CT. Treating doctors were Dr. Jason Williams in Bogota, Dr. Mark Rosenberg in the U.S. and Dr. Leonardo Gonzalez at a clinic in Columbia. Reference.

In many cases, after the first 3BP IV administration, a reduction in pain has been observed.

Note: also to my knowledge there were patients treated with 3BP and not responding. As we will see below, besides administrating 3BP in the right way, the key for 3BP action is the expression of MCT1 which if not present may also be forced with various supporting treatments.

Mechanism

3BP is generally presented as an inhibitor of glycolysis (one of the major mechanisms for energy production in cancer) and has shown remarkable efficacy in not only preventing tumor growth, but even eradicating existent tumors in animal studies and in humans. Its mechanism of action is still a matter of debate but in general it is believed to be an alkylating agent, inhibitor of HK2 enzyme, which is essential in cancer cells for both glycolysis and respiration.

In order to get into the cancer cell and inhibit the HK2 enzyme, 3BP seems to use the MCT1 transporter (Ref) which is over expressed in many cancers visible on PET scan. Highly glycolytic cancers are producing a lot of lactate as a result of the high glycolysis. Lactate together with a proton is pushed out of the cancer cell through MCT4 transporters. As a result cancer cells are also pushing out protons in order to maintain their high intracellular pH. In turn this increases the amount of lactic acid (and thus the acidity) around the tumors. In time, if the outside layer of cancer cells have also access to oxygen, they may develop the capability of using lactic acid as a source of energy for the respiration process. This means that they will start directly importing lactate, through a transporter located on their membrane (i.e. MCT1), convert that into pyruvate and use that further to produce ATP. These are the cancer cells that are believed to be sensitive to 3BP. Why? Because 3BP has a chemical structure such that it can be transported through the same transporter (MCT1) through which lactic acid is imported. Since MCT1 is over expressed in cancers, 3BP will selectively be absorbed by the cancer cells (like we discussed not all but those who have MCT1) and will not affect the normal cells. Understanding this mechanism has great implications on how 3BP administration will be supported.

What we can understand from the above is that the acidic environment around the tumors is supporting 3BP effectiveness and treatments of patients with alkaline substances such as NaBic (e.g. Simocini protocol) should be avoided during the 3BP administration. Next to that, oxygen is required for the cell respiration and thus for the existence of tumor cells that are sensitive to 3BP. Of course, we should avoid any inhibitor of the MCT1 transporter. I will discuss them more in the “Antagonists” section below, but some of them are Ibuprofen, Quercetin, Statins, etc.

In some special cases, 3BP may cross BBB (blood brain barrier):
http://dmd.aspetjournals.org/content/35/8/1393.full
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220552/pdf/10510291.pdf   (see page #14)
http://people.healthsciences.ucla.edu/institution/publication-download?publication_id=212759
http://dmd.aspetjournals.org/content/35/8/1393.full
Starvation should help on this line.

3-BP has non-glycolytic targets as well, such as V-ATPases 20, SERCAs 24, Carbonic Anhydrases 51 and HDACs 52 (Ref.)

Here is a nice overview on the relative expression of MCT1 in cancer cell lines (in red box) and their normal tissue of origins (in white box):

MCT1 expression

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530647/bin/NIHMS417628-supplement-1.pdf

In glioblastoma cells, it takes about 3-4 hours to reach a high level of ATP depletion, after the cells were exposed to 3BP: Refrence

Here is a good discussion on “Enhancing 3-Bromopyruvate Toxicity in Tumor Cells By Inducing Hyperglycemia” http://pharmacologia.com/abstract.php?doi=pharmacologia.2013.571.575

Safety/Toxicity

3BP in its raw state is highly acidic.

If the solution to be administered is prepared well, there should be no concerns. People have been treated for months with no issues. No specific side effects are observed. However, note that long term side effects are not expected but also not known.

If the solution is not prepared or administered in the right way, various issues may emerge from inflammation of the veins to anything that an acidic substance may do in the body. This is why both the pH combined with the administration time have to be balanced.

If a cancer treatment is very effective in killing cancer cells, it may trigger an effect called Tumor Lysis Syndrome (TLS) which may include one or more of the following:  a high blood potassium, high blood phosphorus, high blood uric acid and high urine uric acid, low blood calcium, and consequent acute uric acid nephropathy and acute kidney failure. In case this happens, here is what can be done. This applies for any effective treatment including chemotherapy (when that is effective).

Preparation & Administration

Substance used: 3-Bromopyruvic Acid at purity >95%, preferably >98%. CAS Number 1113-59-3.
Depending on purity, at 95% 3BP is orange crystals, and at 100% white crystals. It can be administered topically, nebulized, taken orally, or by IV. Below are the formulations I am aware of and like all the content I share here it comes with my disclaimer:

Topical

– 100mg 3BP mixed with 2ml water (preferably distilled but not necessarily) in a glass vial
– to the above solution add 50mg sodium bicarbonate (NaBic) powder and mix
– to the above solution add 4ml DMSO
– the resulting solution is applied one or several times/day in the tumor area; if the tumor is at the surface, it can be started with one tumor only and observe the reaction – adapt applied dose accordingly

Tools and materials needed for the above:
digital scale that measures 1mg
DMSO – can be found at various sources on the web. Some of the best is claimed to be this one but this should also be fine.
NaBic – can be found at various sources on the web, for example here

Oral

– 2mg/kg to 4mg/kg 3BP (for example, a person of 60kg would need 12omg if he/she intends to use 2mg/kg)
– 3BP is mixed with drinking water until pH of the solution is about 4 (bets is to use water with as little chlorine (Cl) as possible, since Cl is displacing the bromine in the 3BP) – some are using pH as low as 3 and state not to have side effects but I would stay with 4
– drink every morning one hour before eating (some split the dose in two or even in three and take one part in the morning and one in the evening before dinner)
– a few times/week use pre and probiotics as 3BP may also kill teh good gut bacteria
– as with anything I would always start at lower dose, i.e. 0.5mg/kg and build up to the target dose

My understanding is that most of the people have no issues with this – some people may vomit after the first times but that seems to go away after several days (we had no issue with it)

Update 20160104I am aware of 3 major options for the mixture of oral 3BP:

1. distilled water – this will require probably about one liter of water to get about 2mg/kg 3BP to a pH of about 4 to 5 – the drawback of this options is that it has too much water
2. ~100-200 ml distilled water + 2mg/kg 3BP + NaBic enough to get to a pH of about 4
3. ~100 ml commercial water (such as Evian) +2 mg/kg – add water until pH of the resulting solution is 4 to 5 – the drawback of this option (I only now realize) is that it has Cl inside that will displace bromine from 3BP

Tools and materials needed for the above:
digital scale that measures 1mg
pH measurement tool (preferably an electronic version) available on e.g. eBay or Amazon
– optional a system for controlling water composition: http://www.waterstreetstations.com/

Nebulizing

– 44mg 3BP add 5 ml water (distilled if possible or low Cl amount) and mix
– add 30mg sodium bicarbonate powder (to increase the pH) and mix
– add the above solution (5ml water+3BP+NaBic) to 15ml water
– this should lead to a solution with a pH between 6 and 7
– check pH and make sure is not below 6 so that is friendly to the lungs
– we use 5ml of the solution above which is the max that can go into our nebulizer at one time, and add to this 10 drops of DMSO
– the solution above should be OK and represent no danger if the pH is as indicated
– if everything is good the 3BP concentration can be increased as long as the pH is maintained between 6 and 7

Any modification of the dose should be done step by step and the reaction to that observed.

Tools and materials needed for the above:
digital scale that measures 1mg
pH measurement tool (preferably an electronic version) available on e.g. eBay or Amazon
DMSO – can be found at various sources on the web. Some of the best is claimed to be this one but this should also be fine.
NaBic – can be found at various sources on the web, for example here
Nebulizer here is one that we use but any should be good

IV 

Note: My ideas on 3BP treatment strategy is discussed on a different page – click here to get there 🙂

This administration method requires more discussion:

Unbuffered: One way to administrate 3BP is unbuffered, which is the method used in Egypt for the treatment of the melanoma patient (Ref). They saw impressive results and that is a good reference point for the effectiveness of this method. However, because the solution is unbuffered, the administration time has to be longer otherwise the patient will be put in danger. (This is why probably most of the clinics will not use this method since each patient would require to stay longer in the clinic while the clinics prefer shorter times.) I will refer to the target dose where effectiveness is expected but it should always be started at lower doses and increased if no adverse reactions are observed. This is how this can be prepared:

– target dose is 2mg/kg to 2.5mg/kg
– take the 3BP powder as measured with a digital scale and add in a sterile cup/vial. If the choice is 2mg/kg and the patient weighs 60kg, there will be a total of 120mg to be used for an IV
– mix the powder with 20ml sterile water for injection (not saline!)
– when the solution is well mixed (i.e. no 3BP powder visible) take all the solution into a syringe (if we do not have a 20ml syringe we may need to perform this action multiple times but if we have 20ml syringe, we will need to perform it only once).
– take out the used needle and instead put a o.2um sterile filter on the syringe – at the other side of the filter mount a new sterile needle.
– inject this 3BP solution into the 500ml NaCl (saline) bottle/bag (do not reduce to 250ml because it will be even more acidic).
– put aluminum foil around the NaCl bottle/bag so that the exposure to light is limited.
– administer this solution in about 2.5 hours via a port-a-catch/port/PICC (if this solution is administrated via the arm directly into the vein, there may be inflammation developing in time and the veins will not be accessible for IV for long time before they recover) – this time frame should be respected and not shortened.

Buffered (i prefer the un buffered approach):

– target dose is 2 mg/kg – a little higher can be used in the buffered version
– take the 3BP powder as measured with a digital scale and add in a sterile (or very clean) cup/vial. If the choice is 2mg/kg and the patient weighs 60kg, there will be a total of 120mg to be used for an IV
– mix the powder with 20ml sterile water for injection (not saline!)
– when the solution is well mixed (i.e. no 3BP powder visible) take all the solution into a syringe (if we do not have a 20ml syringe you may need to perform this action multiple times but if we have 20ml syringe, you will need to perform it only once).
– take out the used needle and instead put a o.2um sterile filter on the syringe – at the other side of the filter mount a new sterile needle.
– inject this 3BP solution into the 500ml NaCl (saline) bottle (not 250ml because it will be even more acidic) and shake the saline bag gently.
– next, inject NaBic 8.4% solution: for every ~60mg 3BP I use 1ml  NaBic 8.4% solution. Therefore, if 120mg 3BP is used, 2ml NaBic 8.4% solution will have to be added. After that we need to shake the bottle/bag gently. Note that to my knowledge, Dr. Ko doesn’t like to use NaBic. She is using other buffers. However, note that 3BP solutions should never be neutralized with concentrated solutions of strong bases such as NaOH because the high concentration of hydroxide ion directly displaces the bromide, rapidly producing 3HP (Ref.)
– put aluminum foil around the NaCl bottle/bag so that the exposure to light is limited.
– administer this solution in about 2.5 hours via a port-a-catch/port/PICC (if this solution is administered via the arm directly into the vein, there may be inflammation developing in time and the veins will not be accessible for IV for a month or so before they recover) – this time frame should be respected and not shortened.

Note:
– best to prepare the 3BP solution before the IV, and administer asap.
– best to limit the exposure of the solution to light – if possible administer in a room with low intensity of light – we can wrap the saline bag in aluminium foil as well.
– NaBic addition will decrease the stability of 3BP in solution. As a result it is better if we split the dose in two bottles and prepare the second once the first is finished, e.g. if a total of 120mg 3BP is intended to be administrated, first add 60mg 3BP to a saline bag of 250ml and 1ml NaBic 8.4% and administrate in one to one and a half hour and than prepare and administrated the other 60mg 3BP in the same way. In this way we will get the most out of the IV.

Tools and Materials needed for the above:
– digital scale that measures 1mg
– a Port-A-Catch, port or a PICC line installed (administration in the arm is possible according to the Egypt-case but will lead to inflammation soon – not recommended)
– 0.2um sterile filters for syringe
– glass vials to mix 3BP with water for injection, like this or similar
– Of course there is a need for all the typical stuff required for IV like saline (250ml and 500ml bottles), delivery kit, syringes, needles, water for injection. In Germany everything can be ordered online from here 
– Some bottles of NaBic solution 8.4% will also be required – here is an example

Administration Protocol and Treatment Strategy has been discussed on the following page: http://www.cancertreatmentsresearch.com/?p=184

Source & Cost

There are many suppliers selling 3BP on the web, and most is manufactured in China. It is easy to order 3BP on Alibaba but is a bit more difficult to know which source to trust.

I personally believe that the difference between various sources is related to the following:

– manufacturing conditions – that included the environment in which 3BP was produced and the elements that have been used in production. This may be reflected in the purity level and the rest of components that are in the product we ordered, i.e. rest of 3% if the product has 97% purity
– storage conditions – 3BP has to be stored around 4C. I can imagine that not many of them will have the right storage capabilities next to the fact that many from China are not the manufacturers but trading agencies.

I do know some people using Chinese version even for IV, but I would not do that. Myself, I have some Chinese version for backup but always use the western version. It would be best if for IV the source would be at the level of Sigma Aldrich or similar. The difficulty with Sigma is that they only sell it to businesses or academic institutions. So anyone who would like to have Sigma products, has to have a company and a business address (they always first check the address on Google map – that is their first filter) or represent a university. If that is not the case, we may find a friend with a company or somebody working or studying at a university.

In conclusion,
– if we order from China we need to make sure we have a recommended supplier from whom someone else already ordered.
– for IV, western sources is the way (if possible, not only for IV).
– since recently there is also a source (pharmacy) in Europe/Germany who would sell IV ready solution – vial of 200mg at 30 euro – Update September 2016: This option is not available anymore

Regardless of the source, price is so little that it doesn’t need to be discussed here.

Relevant Literature

– Check the reference list on the following section of this site: http://www.cancertreatmentsresearch.com/?p=184
– Thesis from Heidelberg on 3BP killing pancreatic CSC. Reference
– In renal cell carcinoma, ccRCC, the activity of most other pathways than that of glycolysis has been shown to be reduced and is expected to be highly sensitive to 3BP (Ref.)
– A good list from Cancer Cure
– the inhibition of CA-IX (which is easy to be done), in combination with a hexokinase II inhibitor, may be therapeutically useful in patients with HCCs that are aggressively growing in a hypoxic environment (Ref)

Synergists & Antagonists

A good part of my ideas have been discussed in this post and others here.

Synergistic, Complementary or Supporting:  Curcumin, Curcumin22DG, Glutamine Deprivation e.g. Phenyl Butyrate, Chloroquine, Paracetamol/acetaminophen, Methyl Jasmonate, Fasting, Hypoglycemiareduction in extracellular pH enhanced 3-BrPA uptakeButyrate,  Lactate, Ketosis, Exercise, TestosteroneAcetazolamide, Citrate, Citrate2, Rapamycin

Will make tumors more sensitive to chemo due to ATP depletion http://cancerres.aacrjournals.org/content/early/2011/12/20/0008-5472.CAN-11-1674.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/22073292
http://www.ncbi.nlm.nih.gov/pubmed/25372840
Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine http://www.ncbi.nlm.nih.gov/pubmed/25015789
Stalling the engine of resistance: targeting cancer metabolism to overcome therapeutic resistance http://www.ncbi.nlm.nih.gov/pubmed/23610447
http://www.sciencedirect.com/science/article/pii/S1574789108000045
http://www.cancercuremedicine.com/uploads/4/3/7/1/43718009/cancerstem_cells.pdf

Antagonists: All the MCT1 inhibitors such as Quercetin, Luteolin, Atorvastatin (and other statins), Diclofenac, Phloretin, Naringenin, Apigenin, Genistein, Ibuprofen, Silybin, Disulfiram?

What is not clear to me yet is whether those drugs/supplements that will reduce mito ATP production should be used or not. Example of such elements: Metformin, Paw Paw/Graviola, Doxycycline. Some say yes and some not, due to various reasons. To be clarified.

Clinics Treating Patients with 3BP

US: Dayspring Cancer Clinic
My review: Comprehensive treatment around 3BP. Adding various other treatments to increase effectiveness in case sensitivity of specific cancer is not there or is limited. I recommend this clinic.

US: Advanced Rejuvenation Institute
My review: Unknown

Canada: Cancerimmunotherapycentres
My review: Unknown

Forums on 3BP:

Cancer Compass  – Inspire – Longecity

Other relevant links:

Cancer Cure Medicine – Is a Cancer Cure Being SuppressedWehaveacure – TheCancerCure – Cancer Cured, Again – War on Cancer

Reference on formulation and stability (fore more references see http://www.cancertreatmentsresearch.com/?p=184)

The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions

Composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer This invention provides compositions and methods for the treatment of cancer. An inhibitor cocktail buffer includes at least one sugar, a non-potassium containing buffer, and an inhibitor:

1 Water only 0.33
2 Glycerol, 1% 0.34
3 Inositol, 4% 0.44
4 Sorbitol, 55% 0.47
5 Sodium Phosphate, pH 7.4, 0.5 M 0.17
6 All four agents above 1.00

Therapeutics for cancer using 3-bromopyruvate and other selective inhibitors of ATP production The present invention relates to methods of treating a cancerous tumor using selective inhibitors of ATP production. The present invention also relates to pharmaceutical preparations comprising such inhibitors and methods for administering them intraarterially directly to a tumor, as well as methods for identifying compositions that selectively inhibitor ATP production for use in the invention.

Anti-cancer composition and method utilizing 3-bp and liposomal reduced glutathione The invention proposes a method of treatment of cancers exhibiting a CD163 characteristic by a liposomally formulated reduced glutathione. The invention proposes a method of treatment of cancer of a combination of liposomally formulated reduced glutathione to cooperate with an anti-cancer agent 3-bromopyruvate and its analogs Bromopynivic acid and 3-BrOP (3-bromo-2-oxopropionate-l -propyl ester) (collectively “3BP” or “3-BP”) to ameliorate the 3BP side effects and enhance its cancer-killing capacity and enhance the detoxification of the body of dead cancer cell debris.

Compositions and methods for the treatment of cancer The present invention discloses anti-cancer compositions, and associated methods, including an anti-cancer composition comprising: a cellular energy inhibitor having the structure according to formula I wherein X is selected from the group consisting of: a nitro, an imidazole, a halide, sulfonate, a carboxylate, an alkoxide, and amine oxide; and R is selected from the group consisting of: OR′, N(R″)2, C(O)R′″, C1-C6 alkyl, C6-C12 aryl, C1-C6 heteroalkyl, a C6-C12 heteroaryl, H, and an alkali metal; where R′ represents H, alkali metal, C1-C6 alkyl, C6-C12 aryl or C(O)R′″, R″ represents H, C1-C6 alkyl, or C6-C12 aryl, and R′″ represents H, C1-C20 alkyl or C6-C12 aryl. The anti-cancer composition can additionally comprise at least one sugar, which stabilizes the cellular energy inhibitor by substantially preventing the inhibitor from hydrolyzing. Also, the anti-cancer composition can comprise a hexokinase inhibitor. Further, the anti-cancer composition can comprise a biological buffer that is present in an amount sufficient to at least partially deacidify the cellular energy inhibitor and neutralize metabolic by-products of the cellular energy inhibitor.

A composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer

Methods and compositions for administration of 3-halopyruvate and related compounds for the treatment of cancer The present disclosure relates to the discovery that compounds of the invention, particularly 3-bromopyruvate and related compounds, can be safely administered at concentrations effective for the treatment of cancer when formulated with an acidity of greater than or equal to pH of 2 and less than or equal to a pH of 6. Disclosed herein are novel and improved methods and compositions for the treatment ofcancer using 3-halopyruvate and related compounds.

Methods of treatment using 3-bromopyruvate and other selective inhibitors of atp production

Methods of treating tumors having elevated mct1 expression In some aspects, compositions and methods useful for classifying tumor cells, tumor cell lines, or tumors according to predicted sensitivity to 3-bromopyruvate (3-BrPA) are provided. In some aspects, methods of identifying subjects with cancer who are candidates for treatment with 3-BrPA are provided. In some aspects, compositions useful for subjects with cancers that express increased levels of MCT1 are provided. In some aspects, methods of treating subjects with cancers that express increased levels of MCT1 are provided. In some aspects, methods of identifying anti-tumor agents the efficacy of which is at least in part dependent on transporter-mediated uptake are provided.

Method of treating cancer with combinations of histone deacetylase inhibitors (hdac1) substances A method for treating cancer is described using combination therapies comprising the use of hyperbaric oxygen with histone deacetylase inhibitors, with and without glycolytic therapies. The patient is subjected to a hyperbaric environment of substantially pure oxygen. A predetermined dose of one or more HDACI substances is administered to the patient. In addition, glycolitic inhibitors may also be administered. Dosages, pressures, and durations are selected as described herein to have a therapeutic effect on the patient.

Propyl 3-bromo-2-oxopropionate and derivatives as novel anticancer agents The present invention is directed to compositions that inhibit glycolysis, perferentially in cancer. Specifically, the anticancer compositions comprise 3-halo-2-oxopropionate and its derivatives, such as ester derivatives. However, in specific embodiments, the anticancer composition is sodium 3-halo-2-oxopropionate, such as sodium 3-bromo-2-oxopropionate and a stabilizing agent, such as carbonic acid. In particular embodiments, the compositions of the present invention further comprise a metabolic intermediate for normal cells to utilize in a pathway for an alternate energy source, thereby providing protection to normal cells. In other embodiments, the 3-halo-2-oxopropionate or its ester derivative is used in combination with an additional cancer therapy, such as radiation and/or a drug.

Methods of treating tumors having elevated mct1 expression  In some aspects, compositions and methods useful for classifying tumor cells, tumor cell lines, or tumors according to predicted sensitivity to 3-bromopyruvate (3-BrPA) are provided. In some aspects, methods of identifying subjects with cancer who are candidates for treatment with 3-BrPA are provided. In some aspects, compositions useful for subjects with cancers that express increased levels of MCT1 are provided. In some aspects, methods of treating subjects with cancers that express increased levels of MCT1 are provided. In some aspects, methods of identifying anti-tumor agents the efficacy of which is at least in part dependent on transporter-mediated uptake are provided.

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications. https://www.ncbi.nlm.nih.gov/pubmed/27661124

Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC.

Recent (2016) update on 3BP patent: Methods and compositions for administration of 3-halopyruvate and related compounds for the treatment of cancer https://www.google.com/patents/US9492417 indicating combination with Sodium Bicarbonate as a buffer as suitable to balance 3BP acidity and increase the daily dose.

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: http://www.cancertreatmentsresearch.com/?page_id=1794

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171 thoughts on “3 Bromopyruvate

  1. Wow that was strange. I just wrote an incredibly long comment but after I clicked submit
    my comment didn’t appear. Grrrr… well I’m not writing
    all that over again. Regardless, just wanted to say fantastic
    blog!

  2. In regards to your comment about the “alkaline substances not to be used in 3BP treatment” ie; Nabic. Would it be better to not use the Sodium Bicarb to buffer when administering the IV?

    1. Hi Kim, what I would not use is alkaline treatments during the same time such as Natrium (Sodium) Bicarbonate high dose. But as a buffer, we may still need to use alkaline substances to balance the pH of 3BP. That is so small quantity, that would not influence tumor environment. I hope this helps.

  3. Hi Daniel- I want to thank you for taking the time to accumulate and interpret information regarding 3-BP and related therapies. It all sits there frustrating the heck out all of us scratching for a cure in this lifetime.

    Your Donation/PayPal link results in a non-English page. My first suggestion would be to offer a second link to an English page. I’ll post more when I get some time (and donate when I get a translation!)

    Thanks again!

    1. Hi Fred, thank you for your msg and for considering to donate. I just checked and I think it will localize the language and the country of the user. And this something I cannot change in the plugin installed behind. If that is true, I assume you are now in a different country?
      Regarding the content, if you or other readers would like to address more clear some of the points please let me know – feedback always helps.

    2. I was able to donate by going to my own English Paypal and putting in Daniel’s email and marking it “gift.” At least, I hope it worked. I will go check!

      1. Dear Moonlitnight, indeed that worked. Thank you so much for that to you and to David as well, who also donated. I will make sure that the donations will be converted into new knowledge useful to all of us.

  4. I’m currently trying to obtain 3-BP, first through a U.S. supplier (97%, min. order 10g @ $10/g) and as a backup, a Chinese supplier (97%, min. order 1000g @ $.65 to $1/g). I would like to see if anyone wants to purchase with me as 1kg will go a long way. If I can find 10 people looking to stock 100g of 3-BP (while they research what they’ll do with it) let’s find a way to get in touch.

    Daniel, your thoughts regarding U.S. vs. Chinese suppliers would be appreciated. I think the stuff is so cheap it would be more expensive to try to fake it. They advertise assays from 90% to 98%.

    Still trying to translate/donate 🙂

    1. Fred, this weekend I will try to finish the above post and that would include a short discussion on the various sources for 3BP and related prices. But here is my opinion anyway: I agree that the substance is so cheap that it will always probably be what you order. I personally believe that the difference between various sources is related to the following:

      – manufacturing conditions – that included the environment in which 3BP was produced and the elements that have been used in production. This may be reflected in the purity level and the rest of components that are in the product you ordered, i.e. rest of 3% if the product has 97% purity
      – storage conditions – 3BP has to be stored around 4C. I can imagine that not many of them will have the right storage capabilities next to the fact that many from China are not the manufacturers but trading agencies.

      I do know some people using Chinese version even for IV, but I would not do that. Myself, I have some Chinese version for backup but always use the Western version. Note that anyway many of the western suppliers may get it from China but in that case they are going to pick quality manufacturers and products. So, it would be best if for IV the source would be at the level of Sigma Aldrich. The difficulty with Sigma is that they would only sell it to businesses. So anyone who would like to have Sigma products, has to have a company and a business address (they always first check the address on Google map – that is their first filter) or represent a University. If that is not the case, we can always find a friend with a company or somebody we know is working or studying at an University.

      In conclusion,
      – if you order from China make sure you have a recommended supplier from whom someone else already ordered
      – if anyone is considering IV, western sources is the way
      – since recently there is also a source (pharmacy) in Europe/Germany who would sell IV ready solution – vial of 200mg at 30 euro

      Two more points:
      – the price you are suggesting from the US suppliers seems too low to be the Western quality. Check Sigma price and than take that as a guide to get a feeling on the price for 10g.
      – Also note, that one time I ordered from a supplier Adooq Bioscience, and just after the order the were a lot of money stolen from my credit card + the ordered substance never arrived. Nobody would answer an e-mail or call after that (although before ordering they answered an e-mail). So be careful and try to call at least to see if there is a real company behind.

      I hope this helps and answers your question. But if you still have questions let me know.

      Fred, why don’t you create an user? In that way you can always join with the same name. Otherwise, others may use the same name in the future 🙂 The option is in the right upper side of every page (i.e. Log in)

      1. I have a physician friend applying for a Sigma Aldrich account. The current minimum 3-BP order is 10g @ $98.70 or roughly $10/gram. Hopefully, I can order there. The lowest Alibaba price is $650/kg + delivery.

        A little about my wife’s therapies for anyone interested:

        To the normal standard of care for 3c ovarian cancer we have added other at-home therapies. With the help of another friend, a home infusion consultant, we have been infusing high dose IV-C per Univ. of Kansas protocol. We have a hard HBOT chamber in our garage and my wife does that (at pressures from 1.5ata to 2.5ata) along with 1,3-Butanediol (ketone supplement) per Dr. Dominic D’Agostino, Univ. S. Florida. She has been in and out of chemo consisting lately of Gemzar and Cisplatin. Added to that she takes Metformin, Melatonin, Curcumin and on and on. The HBOT has been mentioned in the cancer compass group for potential pretreatment for 3-BP.

        We have been balancing the other therapies trying to find synergy and not get in the way of SOC. It’s been a six year+ battle.

        My wife has an installed portacatheter so we are able to move into any or all of the 3-BP administration methods mentioned on this page and others. This paper, referenced by the Sigma-Aldrich site, is intriguing:

        Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542237/ (nice to know the darn chemo might be good for something!)

        Thanks again for this site.

        1. Fred, have a look here and let me know if you have questions http://www.cancertreatmentsresearch.com/?p=184
          As soon as possible I will share the info I have on Ovarian cancer.
          Now I will start with this: Inhibition of Wnt/β-catenin pathway by niclosamide: a therapeutic target for ovarian cancer.http://www.ncbi.nlm.nih.gov/pubmed/24736023
          Niclosamide is a very powerful anti cancer component with little toxicity – I bought this one from eBay.

          1. Much info to absorb- Thanks again. I’ll re-write it specifically for my wife (deleting things irrelevant to her) as soon as possible. With that in mind, this site won’t let users cut and paste text. It would make the above much easier.

            Everyone’s a complainer 🙂

  5. Daniel,

    I just realized my post violated a wink and a nod rule. You don’t have to post the above. If you want to comment on quality from domestic vs. other 3-BP sources it would be helpful. I can discuss the group purchase elsewhere. -Thanks, Fred

  6. Question: Last week, my husband had a PICC line inserted. We were given two official “lectures” on what could be put through it, i.e. nothing that could jam or affect the tubing. I assume all PICC/IV tubing is the same. On Friday, our naturopath decided to run through the usual 2mg/kg dose of 3BP in a 500 bottle and intentionally left out the buffer. I wasn’t too amused by this unrequested change but now I see it would fit in OK with the unbuffered mix mentioned in this post. However, could unbuffered 3BP affect the PICC line over time? Has anyone any knowledge or experience of this? I doubt it, given that 3BP is relatively new to this group.

    Fred, I don’t thing I know you from the forum, and I wish you and your wife the very best.

    1. I would not expect that for the solution at this dose since the pH is not that bad. But I would be careful not to combine the 3BP solution with DMSO in the same bag since that may indeed interact with tubing.

  7. Hello everybody

    my mother is now on chemotherapy + DCA + supplements and natural protocols

    but i really want to try a better treatments like 3-BP

    i heard about GcMAF and it’s powerful anti-cancer effect

    they say that there is about 350 doctors and clinics in Europe are using it , and it is possible to cure cancer in about 80% of people for about 1 year+ treatment

    the drug name is GOleic , and it’s not very expensive like other cancer drugs

    i really hope to put my mother in a complete remission

    my question is : in your opinion, what is the best options ? 3-BP ? salinomycin ? other strong drug that i don’t know about ?

    about GcMAF , anyone tried it ?

    thanks alot …

    1. Holly shit, (excuse me here).

      GOleic costs 900 Euro here for 2.2ml

      Having said that, dear Emad, i admire all you do for your mother and i wish you both all the best.
      I would be very interested to know how she is feeling now, what you think is working from the things you tried, general information.
      I hope that with Daniel’s help and everyone else here maybe we can all succeed trough collaboration.
      For my mom the only things that seem to have worked are as follows.

      Aspirin, CBD Oil, Ginger Tea, Coffee Enemas, Vegan Diet, Exercise

      Looking forward to hear from you.
      Alex

  8. I heard about GcMAF and it’s powerful anti-cancer effect

    they say that there is about 350 doctors and clinics in Europe are using it , and it can cure about 80% of people for about 1 year treatment

    the drug name is GOleic , and it’s not very expensive like other cancer drugs , do you have any information about it ?

    1. Emad, I do know something about GcMAF but not enough yet to have a scientific discussion on it. I know doctors who are recommending and others who do not and are even against. I know patients who would recommend and others who would not do that. The most balanced statement I heard was from a doctors stating that it can indeed work for smaller tumors. The 80% is a too big claim I think. So I have a mixed feeling about it. Also the GcMAF sources are various and they seem to fight against each other … So, to answer your question, I think it is interesting enough to considered as a treatment (if the cost is not an issue) but that should not be the main treatment. GcMAF is interesting enough, so I will certainly allocate a section in the blog to this one at some point.

  9. Im from india, my father got 3 bromopyruvate through TACE..in liver..activity dropped by 60%. But the activity in portal vein has not dropped. We are planning to have 3 Brp oral, can you let me know about sellers.

        1. Sounds very good, so far. My next questions: What was the dose administrated if you know? Why are you not going forward with the administration? What is the price (for others that may want as well to be treated in Bangalore)?

          A good idea now would be to add to TACE an angiogenesis inhibitor (such as Avastin) and if possible another glycolisis inhibitor (that is not dependent on MCT1). If TACE is not possible anymore, you can still take such inhibitors systemicaly – in that case not Avastin but others such as Thalidomide and others – a few are also suggested on this website. In addition, you may want to discuss with your doctor the addition of Salinomycin IV.

          1. 1. Dosage: 90 to 100mg diluted with 100ml, wes injected through TACE, there is no clarity on exact method of administration. According to doctor dosage was not increased because it was injected into deceased liver wirh cirrhosis.
            2. Procedure cost is around 1600 USD in Bangalore. With patient consent.
            3. Although there no activity in right lobe of liver..activity was visible in portal vein. It seems through TACE tumor in portal vein cannot be reached. After third dose, immunity level of patient deteriorated. Due to this reasons planning to go oral merhod.
            4. Salinomycin is available? It seems it is costly and not easily available

            1. 1. It would be good to know if 3BP has been buffered or not, and if yes with what.
              2. Great. The price is EU is about 4000 euro so 1500 euro is much more accessible. Off course the questions is also about how experienced the doctor is.
              3. You could check with Dr. Williams in USA or Prof. Vogl in Europe if they can address the portal vein
              4. Sal is available at large chemical suppliers. It is indeed expensive but if you can not afford the base version the doctor can always try the salt version (CAS 55721-31-8) which is 10x cheaper
              Like I said before I would no use angiogenesis inhibitors to reduce the chance of growing back.
              To support the liver you may want to use Astragalus, Milk thistle, Hepamerz

        2. Hi Venu,

          Hope you are doing well.

          Can you share some more details about the hospital that you were referring to, like the location and name of the hospital? My father was diagnosed with oral cancer last year and now it has spread to the lymph nodes in the neck. It would be great if you can share the information about the hospital.

          Thanks in Advance.

  10. Do you know how the other patients treated with 3-BP have fared? Might the doctor have given you any
    information about the effectiveness of 3-BP? Are other clinic in India treating with 3-BP?

  11. – It seems other patients are comfortably now.
    From doctor know about one patient who had oral cancer had complete cure in single dose
    Personally know about another liver cancer patient, SUV , activity in liver was significantly decreased in single dosage.

    – There are no other facilities in india which im aware of.

  12. This is amazing!!
    Thank you for your reply.

    Were you quite pleased with the effectiveness of 3-BP for your father’s treatment?
    Have some of the other patients you might be aware of used IV 3-BP?

    There has been a large amount of interest on our thread concerning ccRCC.
    Apparently ccRCC can have very few mitochondria. This should make 3-BP
    especially effective in such patients. Is ccRCC common in India? Might you know of
    any ccRCC patients treated with 3-BP.

    There are many cancer patients interested in your responses.
    Thank you again!

    1. Was surprised on seeing results with 3bp for my father, I’ve not seen any other medicine which showed as effective as 3bp.
      In india there are many ayurvedic, tibetian(we tried this from Dr Yeshi), homeopathy medicines used by many cancer patients(mostly in advanced stage), but not seen any particular therapy which could show results on PET. They talk about comfort of patient before and after and evidence of cure are not documented. Many other crude medicines like Simarouba, cannabis oil were tried by many, none documented as evidence for cure.

      For ccRCC, IMO if 3bp can reach via TACE, it can show results immediately. Not sure though, about sensitiveness of area where tumour resides, toxivity of 3bp can lead to other issues.

      1. Venu, I suspect that the 3BP received by your father was not buffered. Try to contact dr. Ko – maybe she can support with the buffered version which should not induce damage to the normal cells. Having patients that respond will also be bennefical for Dr. Ko in the quest to demonstrated the effectivness of 3BP.

  13. My father was suffering from stage 4 pancreatic cancer metastasis to liver and lungs. His age is 65 and he is normally active. He was given 3 cycles of chemo (gemicitabine+nab-paclitaxel). But his tumor has grown bigger and so they stopped the chemo and now they have started Oxiplatin and capecitabine. And also we were told that this useless and will not show any improvement so next is palliative care. I gone thru this 3BP in cancercompass and had an idea to enquire about this. Please let me know any of your suggestions and comments

    1. Dear Banu, I am sorry to hear that. For 3BP you may want to get in contact with Venu who posted above and learn more about his experience with 3BP delivered via TACE in India. TACE can deliver 3BP at least to liver and lungs. In addition to that, I would seriously consider Salinomycin that should be accessible and may work very well, even more when combined with chemo that you mentioned above. For that, I will send to you via private the contact details of an Indian lady who is now looking into ways to acess Salinomycin treatment in India.

  14. Thought I’d bring this here, Daniel€¦

    In the course of preparing IV-C solutions I’ve been using .2 micron syringe filters going into the 500ml bag. While sodium ascorbate solutions are bactericidal other solutions aren’t so, to be safe, I’ve been looking at placing the filter after the bag in the IV line. A quick search of McGuff finds .2 micron filtered IV sets at around $2.50 ea. The lowest cost unfiltered IV sets are $1.45 ea. The difference is $1.05. I can’t find sterile Whatman .22 micron syringe filters anywhere near $1.05 ea. so the filtered IV set seems like a win/win- cheap/safe.

    I know my sterile techniques are better than some of my wife’s chemo nurses who throw tubing, connections and syringes around with reckless abandon but always trying to make it better. We’re starting to use her port-a-cath and keeping a sterile system there is even more important than at a peripheral catheter.

    1. Mark,

      Very much interested. Sigma seems hopeless and two other domestic suppliers are tightening their security. Daniel has two Chinese suppliers he trusts and I know of at least two people, already purchasing from U.S. suppliers that might be able to send to people like you and me (nothing illegal there).

      A little busy with grandkids this weekend but we can toss this around later this week. I’ve been frustrated so far trying to obtain 3BP for my wife.

  15. Fred,

    Thanks for the update. Please keep me posted on any opportunities for a group buy in the U.S. I just ordered 5g for a high price from sciencelab.com. At least they seem to be willing to sell to individuals.

  16. For those intending to treat at home please pay attention to the quality of the 3BP API (Active Pharmaceutical Ingredient or Drug Substance as it is called in the US) particularly if you intend to use it intravenously or inhaled using a nebulizer. Check the Certificate of Analysis for that batch if it has been tested for Bacterial Endotoxins (LAL test). Endotoxinemia is a life-threatening state with fever, inflammation, shock, complement activation, strong immune response with depleted coagulation factors causing hemorrhaging.
    Remember that US/EU pharmacopoeial grades don€™t necessarily mean low-endotoxin grades or even endotoxin-controlled grades. So it may be wise to specify a low-endotoxin or parenteral grade of 3BP when ordering.
    See article in Pharma News entitled How Do You Set Endotoxin Specs on API?
    http://rmcpharmanews.blogspot.se/2010/03/how-do-you-set-endotoxin-specs-on-api.html
    If used in topical applications or rectally as suppositories, the highest parenteral grade is not needed and a compendial grade would be acceptable.

    1. Thank you for the suggestions Nina! Indeed this is very important. On this line, when getting 3BP from Chinese suppliers, even if we get a nice and clean COA I would still consider this risk for IV delivery.

  17. Dear Daniel,

    I am living in Hong Kong and am very much interested in 3BP. Would you please let me have the information about your source of supply. Many thanks for your help.

    Best Regards,
    Albert Leung

  18. My 2 cents:
    1. 3BP is Br-CH2-CO-COOH with pKa 1.84. In the presence of hydroxide ion (OH-), the bromine leaves even before the hydrogen of the COOH leaves in an Sn2 reaction. In other words, as soon as you put 3BP in water, Bromine leaves, leaving pyruvic acid behind. This defeats the purpose of taking 3BP, because in order to be selectively taken up by MCT1 and kills the metabolic pathways as a non-specific alkylating agent, you would want bromine sticking together with the pyruvate, not as a freely liberated bromine. The latter would not be preferentially taken up by MCT1-overexpressing cancer cells. As a molecular akylating agent, it won’t be much different than Platinum molecule in cisplatin or carboplatin. Bottom line: you must use an adequate buffering agent to keep 3BP to what it is while it is being injected.
    2. Buffering agents without large quantities of sugar molecules won’t do much as the buffer would be diluted quickly once injected in the body. With sugars around it, the hydrogen molecules and the ring structure provides some level of insulation, buying a bit more time before rapid degradation of 3BP sets in. It’s not much of a protection, but every second counts.
    3. Perhaps stating the obvious, but, you must have a central IV port line. Any peripheral IV will do a lot of damage to the vessels, as the solution is caustic.
    4. I strongly recommend using it under physician’s supervision, unless you are using it at low dose as a maintenance. Tumor lysis syndrome is of known concern, as 3BP kills very rapidly. This is especially true for patients with large tumor burden. Also, blood ammonia toxicity is something you would want a doctor to watch out for.
    5. I’ve seen some very high doses in the post. Just for you to know, the published LD50 (lethal dose) for 3BP in mouse is 72 mg/kg of body weight.

  19. Tom, Thank you for your very valuable comments.
    My comments questions:
    1. A good paper on 3BP stability is here https://www.researchgate.net/publication/265018726_The_antitumor_agent_3-bromopyruvate_has_a_short_half-life_at_physiological_conditions
    Indeed, this indicates that high concentration of hydroxide ion directly displaces the bromide rapidly producing 3-HP.
    On the other hand there are various indications (from opinions to facts) on 3BP as being stable for a limited time in water for injection at the low pH and low temperature. For example, dr. Ko’s patent is indicating some stability (less than one hour at 37 degrees C) of 3BP in water: https://www.google.com/patents/US7754693?dq=bromopyruvate+Sorbitol,+55%25&hl=en&sa=X&ved=0ahUKEwizhtbD7e_JAhWHLg8KHY1vAs4Q6AEIHTAA Indeed, to improve stability she is using sugar as you also indicated.
    Do you have references to indicate that 3BP in water leads to direct displacement of bromide?
    2. I agree.
    3. I agree
    4. If formulated to be highly effective than I agree
    5. I agree and this is why I always stay around a few mg/kg so I was wondering what do you mean by “I’ve seen some very high doses in the post”? Could you please indicate so that I make a correction? Or you are pointing to other posts outside this website?
    Finally, if you have a better formulation method in mind would you please share that here?

    1. Daniel,
      1. Thanks for the paper. No, I don’t have a reference. But it’s a pretty well established rule on the order of leaving groups. In the presence of NaOH, as you warned not to use, the dissociation would be faster. In water, it would be slower. Nonetheless, the hydrolysis is inevitable. The point is, why not avoid the avoidable by using proper buffer. Dripping the IV in an unbuffered solution for 30 min, I would imagine the loss would not be negligible.
      5. I was referring to 10 mg/kg oral, and the one use you warned about, 1 g/day nebulizer user.
      As to the formulation, I do not want to unintentionally encourage people experimenting with their lives. I would strongly suggest them to see a doctor. Of the two places you recommended, dayspring and wellness4cancer, I called dayspring. The rep said their offer wasn’t part of a clinical trial. So I have no clue how they can even offer the treatment without FDA involved. Perhaps they got some sort of permission from the state’s medical board? I don’t know. The one in the Bahamas seems to have a clinical study. http://wellness4cancer.com/research/metablox/

      1. Tom, with the formulation I was/am using is a trade off that accepts lower stability vs more simple formulation. There are cases where it was effective so that is a reference point for me. Beyond that, if I would be a clinic I would certainly improve that but when representing a patient only you need to fly across things and take what you need and move forward. Yes, there is loss when dripping the solution. This is why I mix in two smaller saline bags and mix the second only when the first was finished.
        I will remove the reference to the guy using 1 g/day as it may be missleading for the reader.
        I strongly suggest anyone to see a doctor. Just that we are a case which doctors cannot help and the info I share here is a result of my search trying to do what the medicine doesn’t do for us, unfortunately …
        Dayspring is probably the only place where I would go for 3BP treatments. Otherwise (if there is time to wait) I would wait for some step dr. Ko will probably do soon.

  20. Daniel,

    It appears Dr. Young Ko is starting to make a move:

    http://www.3bpko.com

    “Welcome to Dr. Young Ko’s official 3BP (3-Bromopyruvate) website.
    Your source of information for 3BP.

    Click here to sign up for our newsletter to stay informed about upcoming scientific articles, clinical trials and clinics outside the USA which may be offering 3BP treatment in the future.

    Please note: 3BP has not yet been approved by the FDA, but will soon be undergoing clinical trials. We recommend to not get 3BP treatments by any non-certified facility which is offering 3BP treatments. The use of 3BP and its current indications is patented by Dr. Ko. Any unauthorized use may evoke patent infringement.”

    1. Actually, no company will sue you until the time they want to start selling it, themselves(FDA approval).

      About salty version of DCA which is have lots online sellers, probably it have current patent (salt version), but I am not sure about example I mentioned

  21. Can 3bp work for bile duct cancer? The actual source, or tumor, has not been found yet. My friend is finishing his last chemo treatment today and is heading to CTCA in Illinois for a second opinion. Should we look into a clinic offering this kind of treatment? It sounds more promising than anything he’s been told to this point.

    1. Hi Allison, in theory it can work for all cancers visible on PET. In practice, that remains to be validated. Here is my view on top treatments http://www.cancertreatmentsresearch.com/?cat=1. Although expensive, I suggest you contact dr. Jason Williams and ask him what he can do for you http://www.cancertreatmentsresearch.com/?page_id=409. He seems to have his hands on some of the best treatment tools while being very knowledgeable. He has access to most of the things you can imagine including 3BP. That is what I would do. If you specifically want 3BP only, than the best place in US to my knowledge is the Dayspring Clinic.

  22. Dear Venu
    kindly let me know the hospital in Bangalore and its contact no for treatment of ovarian cancer matastasis in liver and abdomen.

    Thanks and regards

    Rajiv Bedi
    09316055865

  23. Dear Daniel,
    I am an advanced prostate cancer sufferer and would value your opinion on the efficacy of rectal administration of a 10 ml solution of 140 mg of 3BP plus 70 mg of sodium bicarbonate per day at pH 3 to 4. I am 70 kg in weight.
    Regards, ernemef.

  24. Hi Ern, I have no experience with the rectal administration. However, I do know that some clinics are using it. Regarding the numbers you mentioned above, I am only wondering if pH 3-4 is not too low. So I guess you want to check the literature and find what is in general the acceptable pH level for the solutions administrated via the rectal route.

    1. Thanks for the reply Daniel,
      I will search the literature for more info. I chose the values of 3-4 pH because I believe oral ingestion of liquids (soft-drinks) is sometimes as low as that and it gives more time for preparation before loss of activity of 3-BP occurs. However no problem, it can easily be raised. I am really more concerned with the effect of a sudden introduction of this rather concentrated solution, even though it is only a small volume. I guess this may be a matter of experiment with smaller amounts of active ingredient at first.

      Regards,
      ernemef.

      1. Dear Ern,

        you are right: I would always start with lower amount and lower concentration. I also checked some of my notes and I see that the clinics using it in this form (enema) are diluting 3BP in 250ml water. As I mentioned the water should not contain Cl.

        Kind regards,
        Daniel

  25. Great blog Daniel.

    One question I have is the concern of having chlorine (sodium hypochlorite Na+ ClO-) in the water for oral treatments. It says that it might replace the bromine in the 3BP. I take it then that normal chloride (Cl-), as found in our stomach (our stomach acids are mostly hydrochloric acid – HC) will not affect it? I say this because for the IV treatment it is also suggested to put the 3BP in a NaCl solution.

    1. Thanks Cesar. I would have to look back at the research and the reasons behind but the idea was that taking this approach for the mixture will lead to a slower bromine displacement which will anyway happen with time.
      Nevertheless, you can test yourself the stability as a function of Cl content or function of temperature, or function of pH (by adding e.g. NaOH to increase the pH). When the bromine is displaced the substances turns into a brownish solution. A solution of 100mg 3BP in 5ml water should be right for the experiments to see it turning into yellow-brown color.

  26. Hi Daniel, I am Chitrita. I live in the US with my husband in upstate South Carolina. My father is in India and has been diagnosed with state 4 pancreatic cancer with lesions seen in liver and spleen. How can I arrange for him to get 3bp treatment, please help, any comment would be greatly appreciated. Can I contact you by email to get some personalized advice?

  27. Hi Chitrita. Just send me an e-mail and I will send back a few e-mail addresses of people from India treated at a hospital in India. Maybe they can help you finding the right source in India.

  28. Hi Daniel, Thank you very much for your prompt reply. I wanted to send you an email, but couldn’t find your email address on this page. I am sorry if this is naive of me, highly stressed right now. How do I send you an email?

  29. Hi Daniel,
    My wife has recently been diagnosed with multiple myeloma, cancer of the blood plasma. Is 3BP effective on this non lumps and bumps type cancer?

    Ted

    1. Hi Ted, I am sorry. As long as it is visible on PET scan there is potential for effectiveness. Here are a few (very good) articles suggesting that there is high potential of 3BP against multiple myeloma:

      Killing multiple myeloma cells with the small molecule 3-bromopyruvate: implications for therapy. http://www.ncbi.nlm.nih.gov/pubmed/24557015
      The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

      Up-regulation of hexokinaseII in myeloma cells: targeting myeloma cells with 3-bromopyruvate.http://www.ncbi.nlm.nih.gov/pubmed/22298254
      Hexokinase II (HKII), a key enzyme of glycolysis, is widely over-expressed in cancer cells. However, HKII levels and its roles in ATP production and ATP-dependent cellular process have not been well studied in hematopoietic malignant cells including multiple myeloma (MM) cells.We demonstrate herein that HKII is constitutively over-expressed in MM cells. 3-bromopyruvate (3BrPA), an inhibitor of HKII, promptly and substantially suppresses ATP production and induces cell death in MM cells. Interestingly, cocultures with osteoclasts (OCs) but not bone marrow stromal cells (BMSCs) enhanced the phosphorylation of Akt along with an increase in HKII levels and lactate production in MM cells. The enhancement of HKII levels and lactate production in MM cells by OCs were mostly abrogated by the PI3K inhibitor LY294002, suggesting activation of glycolysis in MM cells by OCs via the PI3K-Akt-HKII pathway. Although BMSCs and OCs stimulate MM cell growth and survival, 3BrPA induces cell death in MM cells even in cocultures with OCs as well as BMSCs. Furthermore, 3BrPA was able to diminish ATP-dependent ABC transporter activity to restore drug retention in MM cells in the presence of OCs. These results may underpin possible clinical application of 3BrPA in patients with MM.

  30. Hi Daniel,

    I’m waiting on Quercetin and Salinomycin shipments so in between I want to try IV 3BP. I’ve done oral but that isn’t available right now. Reading comments I’m not sure about the effectiveness of buffered versus unbuffered IV. Both methods seem to be supported. I’m comfortable doing either. Do you have a recent bottom line opinion as to your preferred method?

    Thanks

  31. Daniel, your thoughts as to whether it is possible to use different administration methods concurrently. For example IV 100mg PLUS topical 100mg or 44mg nebulizer? Would it be getting close to toxicity, lysis…?

  32. Waiting on a bulk Sal order for 3 weeks so trying to keep my VIP (Very Important Patient) walking, talking and eating until then 🙂 Thanks as always!

  33. Hello Daniel –
    My husband has stage 4 lung cancer.
    Now he’s taking Opdivo for immunotherapy, do you know if 3-BP will interfere with Opdivo?
    And which supplier you use to purchase 3-BP?
    Thanks,
    Tatyana

  34. I would like to order it from Western suppliers, but I don’t know which one. I trust Western more than Chinese. Is there any way you can help me with information which supplier to use?
    Thanks,
    Tatyana

    1. Hi Tatyana. The best supplier is this one http://www.sigmaaldrich.com/catalog/product/aldrich/16490?lang=en&region=NL
      Also, note that to my knowledge, there is only one pharmacy that sells 3BP for human use. That is in Germany and I am questioning the quality of the product since the product is 3BP in solution and since we know 3BP is not very stable in solution (while the expiring date of these products is suggested by the pharmacy to be about one year – as I remember). All the other sources are selling 3BP for research only, not for human use.

      1. Hello-
        Is there any way we can buy it from you, or do you know anybody we can split it with since the supplier sells 1kg. Which is too much for us.
        Thanks,
        Tatyana

        1. HI Tatyana,
          I do not sell or buy 3BP. Maybe someone else will be interested.
          I am surprised you found suppliers selling 1kg only as most (even the Chinese) will sell less …
          Kind regards,
          Daniel

          1. Sigma or the Chinese supplier? Regardless of which one, that is probably just a typical offer at a typical weight but will be willing to offer lower weights as well (at a probably higher price / g).

      1. Hi Alternmed. I can not answer the question if it is safe.
        I can only say that we have use it for long time orally and IV and nebulized and everything was perfect. I can also say that I have heard of multiple people (including medical doctors and scientists) using it for long time orally with no specific issue.
        But I also heard of people who vomited after using it orally. Nothing else then that.
        Only a clinical trial could give us an exact view on its safety.
        But based on all the facts, 3BP remains one of my favorites.

  35. Hi Daniel,
    For unbuffered IV administration you wrote “inject this 3BP solution into 500ml NaCl (saline) bottle/bag”
    I don’t have access to saline just NaCl IV bag (9mg/ml), is it okay to use that? I also have 500ml with Ringer-Acetat solution.

    Kind Regards
    -entery

      1. Thank you very much Daniel,
        Then it seems like I have the right stuff (it’s just not named saline… just NaCl 9mg/ml from Braun).
        I will try the unbuffered IV protocol and start with 1mg/kg and slowly increase to target dose. I have a port-a-cath installed right next to the tumor site, so hopefully it will have some effects.. Anyway, thanks a lot for providing this information.

        Kind Regards
        -entery

        1. Hi Entery,

          When we started we started with 0.25mg/kg, just to make sure there is no unexpected reaction.
          As we became confident on it, we increased the dose step by step to the target dose of 2mg/kg. That would be 100mg in total for someone of 50kg.

          We found the use of 3BP safe as long as we used that dose, and administration time of about 2h and a total of 500ml NaCl solution for that amount. We never had an issue with this dose when used via the port. But this is our own experience and I can not state that it will apply to all the other people.

          Note and warning: I do know someone who made a mistake and used the wrong digital scale that has 10mg sensitivity instead of 1mg sensitivity. She thought she was using 50mg 3BP but actually she was using 500mg. My conclusion is that clever but inexperienced people can make mistakes. This is why I think a doctor with experience should be involved when stepping in to new treatments.

          Kind regards,
          Daniel

          1. Thanks a lot for the advice,
            I will keep that in mind, and probably start with 0.25mg/kg myself too.
            And I will make sure that my digital scale have 1mg sensitivity.

            Wish you all the best Daniel, and I’m so sorry for your big loss.
            Kind Regards
            -entery

    1. The 3BP used in the research discussed above is the substance with CAS number: 1113-59-3.
      Please make sure you are 100% you have the right substance in your hands. If unsure, I would check with the supplier and if still unclear I would better throw it away. I would not play with this.

  36. Hi Daniel,

    I hope you’re well and continuing the fight.

    Something has been bugging me about 3BP and I just put my finger on it.

    As I recall, the original Dr. Ko 3BP study involved intra-arterial or direct injection to the various tumors. After the astounding initial kill, the mice were allowed to live out their lives and the cancer NEVER returned. My question is, with the massive tumors and probable extensive metastasis, what happened to all the remote sites? How did treatment of the primary tumor(s) stop all progression of metastatic disease? Was the study cancer incapable of metastasis? Or, was there a byproduct of the primary tumor kill that circulated and killed all metastatic disease?

    Your thoughts?

    1. If we gave some of our energy for searching 3BP,i am sure we have seen some very good responces.
      I have good feelings about 3BP and this post will reach 1000 messages before the others.
      Because some of our friends are going to begin this treatment soon.(including me,when drugs arrive)

      1. I hope these will be valuable comments. Take care with it as people around the world are also making mistakes with it. Better, check with the clinics in Turkey. I have strong reasons to believe there is one clinic there working with some of the best on this subject.

    2. Hi Fred,

      Very nice to hear from you. My plans remain the same indeed.

      Regarding your question, in their first study published in 2002 https://www.ncbi.nlm.nih.gov/pubmed/12124317 they indeed targeted first the liver effectively but the animals developed lung mets. So what they did next was to also administer systemic 3BP which suppressed the lung mets as well. here is a quote of the conclusion:

      “In summary, we commenced this study with the objective of testing a novel strategy for the treatment of liver cancer, a strategy that envisioned direct intraarterial injection of 3-BrPA, a potent inhibitor of cell ATP production. We have shown that this strategy is highly effective, reducing in a single injection the total number of viable cells in liver-implanted rabbit tumors to as low as 10% without doing any apparent harm to the animals or their major tissues. As an unexpected extension of our original objective, we have shown also that systemic delivery of 3-BrPA to the same animals bearing the liver-implanted tumors, also does no apparent harm to the animals or their major tissues, but suppresses secondary metastatic tumors that appear in the lungs. Thus, it is possible with a single, carefully selected known chemical agent, and a combination of intraarterial and systemic delivery methods, to inflict extensive damage on both a primary tumor and a secondary metastatic tumor within the same host without doing noticeable harm to the host.”

      I hope this answers your question. How are you Fred?

      Kind regards,
      Daniel

  37. Hi Daniel,
    When we search for efficiency,it is perfect on mice(direct injection on tumor).Again an ACID.
    We have to talk more on safety other than efficiency.You are totally right.After a little bit searching,it sounds dangerous.
    Will it be the drug that will stay in our refrigerator for last chance use?
    Where did you hear that clinic which uses 3BP?.I think they are using it secretly because i couldnt find it on internet.
    Our previous clinic has 3BP but as far as i know they are not using it.
    May be they put some in iv bag:) and dont talk about it.Who knows.
    Kind Regards
    Ergin

      1. Yes, Ergin, 3BP is one of those I studied most intensively and I am most proud of it. We started from zero on it (in 2014) so I had to collect the pieces of the puzzle from allover the world, piece by piece. You can get a feeling on how I started to collect and share what I was learning when you read the cancer compass thread on 3BP. On this road I’ve got in contact with the most knowledgeable scientist and doctors researching or using 3BP across this world. Most of the accumulated info is consolidated in the post above and the related posts that followed this one. My wife wanted to use it and she and I were very happy with it as it was of great help to us. We use it for about 1.5 years and we would have use it for longer if we would have know how to, earlier. But at that time there were only a few places in the world using it and they would not share the know how since that represented their unique added value. It took a lot of time and work for me to consolidate the above and I knew that by sharing my knowledge clinics around the world will start making money out of it. That is what happens today as I know there are clinics across the world using the info from here (and not even sending a “thank you” msg. for the share). However, I decide to share what I know since in the end those clinics may help some people as well, while doing their business.

    1. Hi Ergin,

      In my view and based on my personal experience 3BP is not dangerous but the people using it can be dangerous. Anything that we put in our blood can be dangerous may be dangerous if not done properly.

      Kind regards,
      Daniel

    1. Hi Fred. It’s nice to hear that. We have no choice other than going forward, unfortunately …
      Indeed, the mistake or unlucky coincidence that happened last summer has placed 3BP under negative spot light. It is not clear what was the origin of that given that the clinic was working with 3BP (in some cases with good results) for more than one year, and nothing like that happened. Maybe other treatments they did, maybe TLS, maybe something else. In any-case, it is interesting to see how the world reacts to such a negative news with an unknown cause, and how the world (not) reacted to the news when the liver cancer patient saw great results after using 3BP while conventional methods could not help. A friend was telling me a few days ago that the human mind is 10x more primed to react to negative events as compared to positive events. Immediately, 3BP was the example that came into my mind, supporting that statement …

      1. I agree totally, Daniel. I wasn’t aware of the news story above so I thought I’d present it as a reminder to all to be careful when navigating uncharted waters. My experiences with Salinomycin last year come to mind. The dosage/delivery of maximum effectiveness was just a kiss away from very scary side effects.

        1. Fred, the Bracht story is in evolution and the news reports from last August might now not accurately reflect the current state of the investigation.

          Some of the German language reports have recently used phrases such as “Vorsätzlich” and “am Sande zu lassen” to describe
          the inquiry. {Sie, Might need to brush up on your German.} The report was expected at the end of March, so hopefully we will know more soon.

        2. Hi Fred, I actually now realize that I should add a note on that in my post above. Although I do not believe that the normal usage of 3BP would have led to such negative results, I think is fair to have all the sides of the story discussed here.

    1. Good question J. We need to understand that in order to understand the selectivity of the POH-3BP to cancer cells, as proposed in the recent article you cited. 3-BP transport is very well known to me but POH transport into the cell not. We need to research that. I am sure it will be relatively easy to find since POH has be often studied due to its anti cancer effects.

      1. Daniel, one question, maybe you know the answer. I have seen your references in terms of the blood brain barrier and 3-bp. from what i understood those articles are rather about the presence of mct-1, 2 and 4 within the brain and spinal cord.

        Does it really mean that 3-bp can cross the BB barrier as a molecule? I am very unsure…

        thanks
        W

        1. Wondering, I would a more definitive answer as well.

          Table 3 of this recent article found that 3-BP was BBB+ (guessing that means positive).
          PMID: 28463978

          Also found it interesting that the Table has it as Ames test toxic. I have been wondering about this question for some
          time. I thought that this would be a good test to try on normal cells of mice that had been dosed with 3-BP. It might show
          to what extent there were off targeting of 3-BP.

          I also found it interesting lately that there are actually MCT-1 receptors at the BBB. This is perhaps not the only way for 3-BP to enter the brain, though it is of note that this is the route that 3-BP needs to enter cancer cells.

        2. Hi Wondering,

          The blood–brain barrier is formed by brain endothelial cells, which are connected by tight junctions. https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier

          Some of the articles refer to these cells as expressing MCTs. For example:

          “The endothelial cells of the blood vessels in the brain have been reported to express MCT1 which probably mediates the transport of lactate and ketone bodies across the blood brain barrier (BBB) [63, 64]. The capacity of the brain to use ketone bodies such as β-hydroxybutyrate was found to increase in starvation and diabetes by 50-60% in rats” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084603/

          This means that in theory, 3BP should be able to access the brain.

          During the long time we used 3BP, we never had any side effects related to the brain.

          Is this answering your question?

          Kind regards,
          Daniel

          1. Thanks D, it does.

            You know, there is a credible ncbi study claiming it does not which is being referenced a lot but on the other hand there is contrad. Info. Now i agree it should.

  38. I am pretty much locked into the homeeville Anglo webspace.
    Might others from different regions of global cyberspace chime in on what they are seeing when they search for 3-BP info that is local to where they are from?

    I have been trying to break into different regional webspaces to see their point of view on 3-BP, though often I seem to get bounced back to here or the Compass etc. .

    Would love to know what the local opinion might be of 3-BP globally. Might also be able to pick up on reports for other clinics that have been outside of our search engine range.

    1. Hi J, I heard there are more clinics using 3BP across the world, including US and Europe (and that is only what I know of). But typically, they seems to prefer doing that without advertising it. That is probably due to the negative story from the German clinic. However, what is good is to see that despite the negative news on that specific German case, clinics from around the world are not stepping back from using it. I can imagine this would be the case only if they experienced good added value.

      1. Yes, D I have been looking around on the internet and I found documents about the corporate structure in which Dayspring is associated. I had not realized but Dayspring is actually part of a global company. Their website does not highlight this.

        The corporation has other facilities one of which is in Asia. It is however not entirely clear whether other branches also treat with 3-BP. Perhaps we could ask around on this thread and elsewhere to find out.

        When these higher level corporate structures exist, one would have the impression that knowledge would be leveraged from one part of the organization to another. If you were to have only one isolated clinic, then you think that there would be a tendency to protect information gained. I find it encouraging to realize that a global company would be positive about 3-BP.

        Any word on the investigation?

          1. Wondering thank you very much for your update from German media!

            I am sure that the Bracht investigation report will be widely reported in Germany and I am very anxious to hear your reports when the news breaks. From the non-German perspective, I am not sure whether this news will be carried. When the tragedy occurred there was saturation online coverage, though if the inquiry were to report a more nuanced and ambiguous conclusion, media simply might not report it. Media are typically only interested when the fire trucks have their sirens and flashers on.

        1. Ok, I looked this up again. This is a tad nebulous.

          This first url is for Biomaxx Holdings Limited.
          They have corporate locations of Teufen, Switzerland and Hong Kong.

          The below pdf describes Dayspring’s use of 3-BP without actually clarifying whether Dayspring is a Matryx Cancer Clinic or part of the Matryx Center Network.

          http://www.biomaxx-holding.com/PDF/Bromopyruvate-Infusion.pdf

          I then find this again named as mithrabiomaxx.
          http://www.mithrabiomaxx.com/cancer-strategy.php

          Under the drop down menu of Single Therapies –> Bioimmune Therapies they have bromopyruvate.
          Under the drop down treatment programs they have for 21 “brompyuvate”

          One of the clinics for Mithrabiomaxx is Brio Clinic Bangkok.
          http://www.mithrabiomaxx.com/PDF/Brio-Clinic-Bangkok.pdf

          While the Biomaxx holdings site listed clinics for Swiss Wartensee, Germany Tübingen and “Other Centers”
          http://www.biomaxx-holding.com/

          They appear to have a keen interest in the financial potential of their initiative (See Financial Requirements on page 3),
          while acknowledging that it might be best to quickly yet discreetly setup their network.

          “It is important to keep the minimum required marketing efforts to below the radar limit of visibility of the pharmaceutical industry.”

          http://www.biomaxx-holding.com/PDF/Investor-Information.pdf

          Anyone ever hear of any of this?

          1. I remember I was looking at this Biomaxx as they claim they also do Diflunisal http://www.biomaxx-holding.com/pHTT.php But somehow, I do not have a feeling of trust when looking at the website. I remember once, someone contacted me who was suggesting on a website (but not claiming) to be a clinic offering most of the relevant treatments. I contacted them, and it was actually one guy ALONE who was behind the website, and offering advice where to go for each of the treatments, depending on the cancer type. So if you would want TACE he would suggest a doctor for that, if you would want 3BP he would maybe suggest Dayspringclinic, etc. I have the feeling that this Biomaxx is essentially the same.

  39. Yes, I am also very unsure about them. I can fully understand how many would want to be part of the 3-BP story, though
    the question of whether they have authorization to provide such treatment is very unclear. It is possible that we are now
    moving towards the start of a clinical trial with 3-BP and more clinics could enter the fray.

    Yet, it is not certain that bringing on board a great number more clinics that do not have a long standing background in 3-BP will
    be of long term benefit. Clinics without the required technical skills might simply create more Brachts.

  40. Dear D, the research up till this point has talked of a possible ROS generation angle to 3-BP as you have noted.

    “Furthermore, our results offer alternative interpretations of 56 previously published models on the role of supplemental antioxidants: Rather than 57 quenching reactive oxygen species (ROS), supplemental NAC or GSH directly interact 58 with 3-BP, thereby neutralizing the drug’s cytotoxic potential before it can trigger ROS 59 production. ”

    “Surprisingly 442 however, in the presence of antioxidants (NAC or GSH) this inhibitory effect was 443 completely prevented, even though these were cell-free reaction conditions without the 444 possibility of free radical production by intact mitochondria or other cellular processes. 445 This outcome suggested that the protective effects of NAC or GSH might not be via their 446 conventional quenching of free radical species. (See Discussion regarding an alternative 447 model explaining cytoprotection by NAC and GSH.)”

    These quotes are form the recent POH article PMID: 28450161.

    It is possible that ROS is not involved with 3-BP efficacy.

      1. Yes, it is confusing in biology when new research is published that contradicts a long line of consistent evidence. Best to wait and see whether the new research is embraced by others.

        It is important because if ROS is not being produced by 3-BP than combining with other ROS generators would not be as effective.

  41. D, I have been posting to the Compass thread about ethyl pyruvate.
    This sounds like it has potential.

    It has been given in a high dose IV phase II trial for high risk cardiac patients where it was not successful, though
    there would seem to be an ATP depletion side of it. It is considered GRAS, yet the one problem noted was that
    it might be very unstable when injected (another reference talked of a Ringer’s solution with EP that was stable).

    I am somewhat surprised how many of these 3-BP like drugs are out there and could have significant anti-cancer effect.
    If they could stabilize EP for human IV dosing at 10 mM then this would be the concentration that resulted in irreversible
    ATP depletion.

      1. Yes, I found it on the FDA’s GRAS list along with methyl jasmonate and others.
        Below snippet is interesting. The Ringer’s EP solution apparently went to 130 mM.
        Leukemia cells were permanently ATP depleted at 10 mM.

        Going with IV EP might make some sense.
        The phase 2 trial found side effects were equal among control and those who received 7,500 mg every 6 hours for a total of 6 doses. It would seem to be a good one and just see if it could do anything.

        Reference

  42. Hi Folks,

    I looked at the suggested websites and it seems there is a clinic in Bangkok, the medical director is called – no kidding – Dr. Porntip 😀 Full name is actually Dr. Porntip Chooparnich Here is the link: http://www.mithrabiomaxx.com/PDF/Brio-Clinic-Bangkok.pdf There is at least one other doctor, with a German sounding name and look.

    I did see the “under the radar” statement, which is very strange. In the roll-down menus of http://www.mithrabiomaxx.com/index.php under “Therapy Programs” at e.g. http://www.mithrabiomaxx.com/basic-programB.php there is something called Chlorin e6 as a photosensitizer. Does anyone know what that could be? Also, do they have a price list?

    Cheers,
    Helga

  43. Hello, greetings to everyone! I am thinking about oral use of 3-BP. And I am worried about bromine displacement by chlorine in the stomach acid. Would capsulation be a good approach to avoid 3-BP degradation? Also, I found info about buffer that stabilizes 3-BP. Is that another reasonable precaution with oral use, or buffering the solution is needed only with i.v. administration? Share your thoughts, thank you!

        1. We do not have studies on the dynamics of 3BP in humans after oral administration. However, the change of 3BP is a function of pH and temperature. Based on experiments done at home, even in extreme pH and temp. conditions, it takes a bit of time for that. On this line, I would expect that at least part of 3BP will be absorbed before displacement. This is also supported by the fact that some people I know did responded to oral 3BP.

  44. Daniel I have 2 questions :-

    1 – why we should mix 3-BP with water instead of NaCl ? I’m used to mix DCA with NaCl before , also today I tried to mix 3-BP with NaCl and it dissolved completely , but I’m not sure what is the issue in the first place , is it about the solubility is poor in NaCl or its not good for its stability ?

    2 – did you see effectiveness when you administrate 3-BP at night ? or you noticed only good respond when you give it in the morning when the patient is still fasting ?

    wish you good weekend for you and all other friends here

    1. Hi Emad,

      The answer to the first question is in the text above. Please check and if you do not find it I will explain.
      Regarding the second questions, I cannot say I have seen a special pattern but that is because we were using it mainly in the evening due to our daily schedule.

      Have a very nice weekend too!

      Kind regards,
      Daniel

      1. Looks like I found the answer when I read some comments above

        I understand the idea that mixing 3-BP with NaCl may lead to faster bromine displacement , in that case I will make sure to mix it with water , but until now I didn’t see the solution changed in color even after 3.5 hours in NaCl , hope its a good sign

        overall , the product I received from Santa Cruz looks excellent

        for the second question , I have the very same problem as I can only give IVs when I am back to home in the evening , hope its fine

        Thank you so much for your answer 🙂

        Kind regards
        Emad

  45. Dear Emad,
    I dont know why but i cannot use my mail.For your question:Yes please,If you could help me with a video,i will be very happy.
    I will create another mail if it will not work next days.
    Bye the way sal and 3-bp is a perfect combination,i like both.Are you using again salt version of sal?My mother had an antibiotic allergy when she was young and we dont know now.I am afraiding to use sal because of it.

    You should look at blood counts as i read after 3-BP.It may be very effective with salinomycin.

    Kind Regards
    Ergin

    1. I will show you how to prepare DCA , the same will go for the others

      but I can’t advise you to go ahead with it , its for only general information not for you to start with it right away

      if you watch this video you will probably not need any other video from me

      https://www.youtube.com/watch?v=aHM_iu18m5E

      also you can search for a lot of videos on youtube

      search for “0.2 um filter” and you will get it all

      yes I’m using salt version of Sal , i don’t know if its like the base version but the side effects are the same

      you need to be careful from allergy , for any reason you should always start on very low doses

      for Sal , its hard , its already small dose its barely visible , you should have some help from experts if you can , its better than having risk doing things by yourself

      I can remember one time i pushed the dose slight more than 0.2mg/kg of Sal and the side effects were strong and it was a scary night to me , but when it comes to cancer , its the only scary thing compared to any other thing in this world

      regarding blood counts , we will not do it right now , we have to see what is happening with scans

      speaking about scan , I’m wish to hear better results about your dear mother soon , i will pray for that

        1. You always welcome brother

          I understand from your comment that you did know how to make any solution sterile and ready for IV

          if you still need a video please ask me

          1. Thanks Emad,everything is clear.I want to use 3BP before phlorizin+hyperthermia.
            I am searching for 3bp cases now,there is not too much on internet.
            Your experience is great for all of us.I hope it works Emad.And T4 depleteion will also work.
            Than we can make combinations.Did you find any other cases with 3bp?
            There is one:they use 3bp with paracetamol(glutathione depletion).
            In some forums they say metformin+3bp causes lactic acidosis.
            I am sure Daniel knows more.

            1. And Emad i wonder if salinomycin worked or not for your mother.
              I think it didnt work,what do you think?May be because of salt version.
              Because while searching,salinomycin is a perfect drug for cancer stem cells especially,
              and Daniel saw very good responce.Did you search for other antibiotics?
              Targeting mitochondria with antibiotics and you can add an anti worm-parasite drug.
              Now you are on a very good and brave protocol.I think the best protocol and i hope very much for it to work.
              Always wishing best for you.

              1. Yes I still didn’t get the desired results from using Sal but also I’m still not aggressive on using it

                in trials they are giving it every second day , I’m still giving it once or twice weekly not more

                I may try other things like anti worm-parasite drugs but just when I can’t see any positive effect from Sal

                its maybe due to salt version not effective but I can’t understand this , they look very similar

                the same shape , the same side effects , the same look and feel and the both cause tremor if this is a sign of a response

                also in the research field they are talking about both of them like they are the very same and no difference between them , I still believe on it whenever I see the good results in articles talking about it

                hope combining it with 3bp will make it strong

                wish the best for you too brother 🙂

  46. Hi Daniel!

    Just checking in and it’s great to see you working this site!

    3BP was mentioned in passing in an article from Yale: “… our team has demonstrated the efficacy of the first anti-glycolytic agent 3-Bromopyruvate (3-BrPA) in several animal models.” http://medicine.yale.edu/lab/radresearch/research.aspx And “… Cancer cells have long been known to exhibit altered energy metabolism. This metabolic phenotype includes a dependence on glycolysis (cytoplasmic) rather than oxidative phosphorylation (mitochondrial respiration) for the production of intracellular energy (e.g. ATP). The biological significance of this altered metabolic phenotype is underscored by its recent classification as one of the hallmarks of cancer.”

    I see Single Cause Single Cure has changed the name to Foundation for Metabolic Cancer Therapies and has recently funded Drs. Pete Pedersen and Thomas Seyfried and others. Looks like metabolic research might be progressing but in the normal slow fashion. It’s nice to see more dollars thrown that way.

    I will never forget you and Miha.

    Take care

    1. Hi Fred,

      I apologize for the delay of my answer as I was on holiday during the past weeks.

      Its great to hear from you! I will never forget you and Linda and whenever I will be near you I will let you know. Also, if you will come close to the Netherlands please let make sure you will visit me as well.

      Interesting to see the link from Yale and to hear about the activities from Single Cause Single Cure. However, in order to really make a change we need many of us to unite across the world. Otherwise it remains a hobby for universities and foundations. I am still thinking about a way to go beyond that.

      Maybe is a good idea to have a Skype call as we intended sometime ago? What do you think? I am usually back from work a little before 19:00 Amsterdam time – after that I can be available.

      Kind regards,
      Daniel

  47. Is there a little chance that IV can take the 3-bp / salinomycin IV infusions for 3 weeks, as is the protocol, without an implanted port?
    It just started for 2 days, today is about to reach the maximum of 3-bp and the hand is already swollen. Do you think that the treatment cycle may end in these conditions?

  48. D, could you help out?

    I have been wondering about the vitamin C 3-bp combo. You noted the possible synergy in your post. What I am interested in is the gsh depletion potential of vitamin C. I thought that one could lead in with a week or two of vitamin C and then start up with the 3-bp. What I am not sure about is whether normal cells would also become gsh depleted. Safety would be a concern if normal cells were depleted. Do you have any references that show that normal cells don’t deplete? I have been looking around, though I have not found anything.

    Noticed that over the last few days there have been some media mentions of Bracht.

    1. HI J,

      Nice to hear from you!

      The more info I come across regarding 3BP, the more I think that GSH is not the main challenge. To me it becomes more and more clear that the transport of 3BP in the cell is the challenge related to its effectiveness. It also becomes clear to me that the relevant MCT transporters are the most expressed in the cells at the surface of the tumors. This is why the best 3BP effectiveness is during/after the first IVs. If the transporters are enough expressed the first IVs can lead to serious response even without GSH depletion. So high that it can become dangerous, specifically for those with advanced cancers and less functional liver. This is where doctors can make mistakes when they start new patients at normal dose (and not small dose). If prior to that patients receive GSH depletion treatments, it can be even more effective and dangerous.

      After the first IVs, response reduces and then we need to focus on MCT up-regulation support. That is also the point when we could consider starting GSH depletion strategies. + treatments to keep under control the remaining tumors.

      Kind regards,
      Daniel

  49. D, Hope you’re having a wonderful summer!

    I am only beginning to appreciate how much larger MCT-1 levels are in ALL progressing cancer patients.
    (0.31–1.09) versus (0.01–0.05)
    For example, Table 4.

    Also ” it can be said that those women with MCT1, MCT4 and CD147 expressions respectively ranging between 0.01–0.05, 0.0005–0.002 and 0.063–0.072 are considered healthy; those whose MCT1, MCT4 and CD147 expression levels respectively ranged between 0.08–0.28, 0.001–0.006 and 0.32–0.37 are cancer patients with low odds of progression; finally, samples with results showing relative expression in MCF7 between 0.31–1.09, 0.03–0.08 and 0.53–0.80 respectively for MCT1,
    MCT4 and CD147 indicate disease with chances of disease progression”

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412261/pdf/ijms-18-00170.pdf

    I had thought that perhaps some patients could have MCT-1 levels as low as those without illness.

    For me, this suggests that 3-BP might help a broad range of patients to deplete their GSH selectively in the cancer cells. It would not even require 3-BP to appear to cause direct cancer cell lysis: 3-BP could simply wear down the GSH in the cancer cells. Afterwards, one could switch to vitamin C possibly with vitamin K3 for the knock out punch.

    Too bad the FDA requires that all treatments need to be shown to be safe and effective!
    Showing only that 3-BP were safe would allow the combo to go forward.
    With the above plan, 3-BP monotherapy would seem totally ineffective, however, when the vitamin C/K3 was added in it could be
    seen to be much more effective.

  50. This was a surprise to me. The study looked at lymphoma cells and some of the cells had very low MCT-1 levels. Not surprisingly this meant that 3-BP was not very effective. What was surprising was that even while 3-BP was not effective 3-BrOP was.

    “Thus, because of its better cell permeability and chemical stability, the ester pro-drug of 3-BrPA, 3-bromo-pyruvate propyl ester (3-BrOP) was used instead. 3-BrOP showed very high citotoxicity at low dosage (Figure ​(Figure2C),2C), suggesting that the ability of 3-BrOP to enter the cells and release 3-BrPA via hydrolysation by cellular esterases accounts for the > 10 fold difference in the potency of the two compounds.”

    Wow! How does 3-BRoP enter a cell that blocks 3-BP entry?

    We need to keep an eye out for these articles because it was not listed using a 3-BP search.
    A considerable amount of 3-BP research flies under the radar.

    Reversal of the glycolytic phenotype of primary effusion lymphoma cells by combined targeting of cellular metabolism and PI3K/Akt/ mTOR signaling

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