Rapalogs: unraveling the journey from Easter Island to human trials

Some 50 years ago, an intriguing chemical compound was discovered by culturing microbes found in the soil of Easter Island (also called Rapa Nui). Named rapamycin to honor its site of origin, the compound was initially shown to inhibit fungal growth. More importantly, it was later found to suppress the immune system. Following decades of drug development, rapamycin became a key immunosuppressant drug for organ transplantation, and its chemical cousins, called “rapalogs,” were later approved for treating many types of cancer. Today, my colleagues and I at Cambrian Bio and Tornado Therapeutics, one of Cambrian’s pipeline companies, believe that rapalogs also hold remarkable promise for new applications, such as treating and preventing diseases of aging including viral infections and cancer.

The story of how we got here involves many twists and turns and I have had a front seat for a significant part of it throughout my career as a medicinal chemist — first at SmithKline Beecham (which later became GSK) more than 30 years ago, and more recently in my roles as Executive Vice President of Chemistry at Cambrian and Chair of the Board of Tornado.

As rapamycin became a component of immunosuppressive therapy in the clinic, scientists — including myself at SmithKline Beecham — were working to engineer a diverse collection of rapalogs to see if rapamycin’s original activities could be altered to improve drug efficacy and safety. These were very exciting efforts, but as often happens in industry, they were eventually abandoned due to shifts in priorities and funding.

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