“Wonder Drug” (15K) for cancer therapy and improving our QOL

Preface

In our long human history, there appeared a series of wonder drugs that have saved millions’ lives. One of the oldest wonder drugs is called propolis, a bee-made antibiotics, that has been used as a traditional medicine over 4000 years since the ancient Egyptian era. Not only healing wounds and inflammatory diseases, it was used to keep the body of deceased royal family intact under Pyramid for almost forever by preparing mummies. Another old wonder drug is called “Aspirin”, a pain-killer developed by a Bayer chemist, from the herbal medicine “salicylic acid”.  The first man-made wonder drug used to be called “606” or “Salvarsan”. It is an aniline dye coupled with arsenate, developed by the 1908 Nobel-laureate Paul Ehrlich in 1909. It kills the syphilis-causing bacteria “Spirohaeta”. Since then Dr. Ehrlich has been remembered as the “father of chemotherapy”. In 1940, MGM made a film entitled “Dr. Ehrlich’s Magic Bullet”.

An old man called “Charlie” in this drama based on the true story entitled “Charlie’s Angels” was inspired by this old film during his student days, and decided to be a scientist, instead of being an artistic painter, to make his own magic bullet killing the formidable cancers. Shortly after the end of WW II, Charlie and his younger sisters were once contracted with a deadly disease called “TB” (tuberculosis), but saved by another wonder drug called PAS (p-aminosalicylate) developed by a Swedish chemist. Charlie’s strong determination for developing his own magic bullet was solidified by these two historic events during his youth.

The wonder drug developed by this international team “Charlie’s Angels” in 21th century is called HT-192 or 15K.  It was synthesized by a young Ph. D. student called “Hideaki” in Japan from an old acidic pain-killer called “Ketorolac”. It was his 192th chemical compounds that he synthesized towards the end of  his 2 years graduate student life under the supervision of Charlie, an old man living in Australia. “K” stands for Ketorolac and "15" is its birth year (2015). 15K is a highly cell-permeable ester of Ketorolac synthesized by a simple cupper-catalyzed reaction called “Click Chemistry” which was originally developed by the 2001 Nobel-laureate (Barry Sharpless). 

This team includes another brilliant young  Ph.D. student called “Binh” from Vietnam. Binh found that the anti-cancer activity of Ketorolac was boosted over 500-fold by this Click Chemistry. Ketorolac is a PAK1-blocker, and its anti-PAK1 activity was also boosted over 500-fold by this esterization. It marked a new "Guinness record" in PAK research!  PAK1 is the major oncogenic/ ageing kinase that Charlie has worked on for 4 decades since his NIH days. This enzyme is required for the growth of cancers (in particular solid tumors) and definitely shortens our lifespan. In other words, PAK1-blockers in general are cancer-killers and elixirs, but causing no side effect. That is the reason why they called 15K a wonder drug, and filed a patent. Interestingly, propolis is also among herbal PAK1-blockers which indeed extend our healthy lifespan. In fact they managed to boost the anti-cancer activity of a propolis ingredient called caffeic acid (CA) over 400-fold by the Click Chemistry as well.

They expected that 15K is worth 200 million dollars, if they can manage to sell the license to pharmaceutical giants such as Roche, Novartis and Pfeizer who are fiercely fighting/racing to develop the very first FDA-approved PAK1-blocker. Interestingly, Ketorolac was developed as a pain-killer by Roche more than 3 decades ago, and recently the 1987 Nobel-laureate (Susumu Tonegawa) managed to sell the license (worth 200 million dollars) on his own PAK1-blocker series (FRA 1234) to Roche. Unfortunately, however, FRA1234 turned out to be both water-insoluble and poorly cell-permeable. 

Thus, Charlie recently decided to develop both water-soluble and highly cell-permeable PAK1- blockers from Ketorolac, and his team eventually succeeded in realizing their own dream by the Click Chemistry. There is no doubt that 15K would pave a smooth path for Barry Sharpless to receive his second Nobel prize, when 15K is successfully marketed as a wonder drug in a decade or so, finally establishing that 1,2,3-triazolyl ester is a powerful cell-permeable vector for the delivery of COOH-bearing drugs.