On the remarkable antitumor properties of fludelone: how we got there.
Small-molecule natural products are presumably often biosynthesized with a view to optimizing their ability to bind to strategic proteins or other biomolecular targets. Although the ultimate setting in which a drug must function may be very different, the use of such natural products as lead compounds can serve as a significant head start in the hunt for new agents of clinical value. Herein we reveal the synergistic relationship between chemical synthesis and drug optimization in the context of our research program around the epothilones: how synthesis led to the discovery of more-potent epothilone derivatives, and discovery inspired the development of new synthetic routes, thus demonstrating the value of target-directed total synthesis in the quest for new substances of material clinical benefit.
Rivkin
Alexey
A
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021, USA.
Chou
Ting-Chao
TC
Danishefsky
Samuel J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D034261:Epothilones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015394:Molecular Structure
D000970:Antineoplastic Agents; D034261:Epothilones; C506241:fludelone