CANCER TREATMENT VIA REPOSITIONED TRICYCLIC ANTI-DEPRESSANT-LIKE DRUGS AS ANTI-CANCER AGENTS AND NEW COMBINATIONS OF SUCH DRUGS
The title above represents the title of a just published patent http://www.freepatentsonline.com/y2018/0133208.html
The authors argue that an intracellular organelle (normally maintaining an acidic pH that are filled with a variety of degradative enzymes including proteases, and believed to function as the garbage disposal) have an important role in tumor invasion.
As a result the authors use imaging screening method to discover compounds that altered the position of intracellular lysosomes. These compounds block outward movement of tumor cells in response to environmental triggers which normally results in an increase in tumor invasion.
The drugs they identified as lysosome migration inhibitor are:
As we can see, the list above contains existing drugs also discussed on this website (such as mebendazole, niclosamide), natural supplements and chemos.
Since this patent is related to lysosomes activity, you may also like to read the post on authophagy inhibitors that are drugs interfering with lysosomes https://www.cancertreatmentsresearch.com/category/authophagy-inhibitors/
More relevant details on the above list (from the patent):
A total of 2240 repurposed and natural product drugs were screened for lysosome migration inhibitors and 18 “hits” were identified where the Z′ score was at least greater than 50%. There was a hit rate of less than one percent, which supports the specificity of the screen. The 18 chemicals indicated as lysosome migration inhibitors, or chemicals which inhibited lysosomal movement away from the nucleus and inhibited dispersal throughout the cytoplasm, and/or promoted lysosomal clustering near the nucleus.
Nine of the hits belong to a class of drug that disrupts microtubules. This is explained by the inventors to because of microtubules playing a major role in movement of lysosomes towards the plasma membrane.
Three of the hits were benzimidazoles (albendazole, fenbendazole and mebendazole) which act as anti-heminthic agents—and are thought to disrupt microtubules in parasites.
Three of the hits were Vinca alkaloids (vindesine, vincristine, and vinorelbine) which are anti-microtubular drugs.
One of the hits was paclitaxel, another microtubular disrupting agent belonging to the taxane class
One of the hits was colchicine, another microtubular disrupting agent, used in gout, irritable bowel syndrome and other maladies.
Finally, the ninth member of hits that target microtubules was podophyllotoxin, a non-alkaloid lignin that has been used against HPV induced warts.
Two of the hits were ergot alkaloids, dihydroergocristine mesylate [(5′α,10α)-9,10-Dihydro-12′-hydroxy-2′-(1-methylethyl)-5′-(phenylmethyl)-ergotaman-3′,6′,18-trione mesylate] and dihydroergotoxine mesylate. These drugs have been used for the treatment of dementia and Alzheimer's.
One of the hits was niclosamide, a beta-phenylbenzamide that uncouples the electron transport chain and is used as an anti-helminthic.
Two of the hits were tricyclic antidepressants (pizotifen malate and deptropine citrate) which act as anti-histamines that are used to treat chronic airway obstruction asthma, migraine headaches and treatment of anxiety.
One of the hits was raloxifene, a benzothiophene used as a selective estrogen receptor modulator.
Another hit was mefloquine, a quinolone derivative that is used to treat malaria. [(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol
Another hit was harmine, a beta-carboline alkaloid used to treat depression.
Another hit was isoquercetin, a flavonoid used in alternative medicine.
A final hit was the compound tetrandrine, a bis-benzylisoquinoline alkaloid and a calcium channel blocker.
Hi Ergin, This is going to be off topic but could you contact me please. I want to ask you few questions. My email adress is [email protected] Thanks