The practical synthesis of a novel and highly potent analogue of bryostatin

J Am Chem Soc. 2002 Nov 20;124(46):13648-9. doi: 10.1021/ja027509+.

Abstract

Macrocycle 1 is a new highly potent analogue of bryostatin 1, a promising anti-cancer agent currently in human clinical trials. In vitro, 1 displays picomolar affinity for PKC and exhibits over 100-fold greater potency than bryostatin 1 when tested against various human cancer cell lines. Macrocycle 1 can be generated in clinically required amounts by chemical synthesis in only 19 steps (LLS) and represents a new clinical lead for the treatment of cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Bryostatins
  • Drug Screening Assays, Antitumor
  • Humans
  • Lactones / chemical synthesis*
  • Lactones / metabolism
  • Lactones / pharmacology
  • Macrolides
  • Protein Kinase C / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Bryostatins
  • Lactones
  • Macrolides
  • bryostatin 1
  • Protein Kinase C