All chapters

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
2014
Print ISBN
978-1-84973-806-4
PDF eISBN
978-1-78262-420-2
ePub eISBN
978-1-78262-290-1

From the book series:
Drug Discovery