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Chapter 12

Unleashing the Power of Semi-Synthesis: The Discovery of Torisel®

Natural products offer unique and creative opportunities for drug discovery. With their complex architecture and multi-faceted functionality, these secondary metabolites often display exquisite pharmacological profiles and properties. Accordingly, natural products provide versatile and innovative starting points to apply the tenets of medicinal chemistry. Rapamycin (Rapamune®) is a potent, polyketide immunosuppressive agent, produced by Streptomyces hygroscopicus. Rapamycin forms a complex with FKBP and mTOR that elicits its unique mechanism of action, central in a number of biological processes. It is approved for the treatment of transplantation rejection. As part of a programme aimed at the identification of novel rapamycin analogues, we have explored systematic semi-synthetic point modifications to functional groups at essential regions of the molecule. The medicinal chemistry design rationale and strategy is highlighted, culminating in the discovery of CCI-779 (temsirolimus, Torisel®). Torisel® was approved (USA, May 2007) for the treatment of advanced renal cell carcinoma.

Publication details

Print publication date
14 Aug 2014
Copyright year
Print ISBN
ePub eISBN

From the book series:
Drug Discovery