Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

  • J Med Chem. 2009 Mar 26;52(6):1518-21. doi: 10.1021/jm900012a.
Hugo G Menzella  1 ,  Thomas-Toan Tran ,  John R Carney ,  Janice Lau-Wee ,  Jorge Galazzo ,  Christopher D Reeves ,  Christopher Carreras ,  Sophie Mukadam ,  Sara Eng ,  Ziyang Zhong ,  Pieter B M W M Timmermans ,  Sumati Murli ,  Gary W Ashley
Affiliations
  • 1. Kosan Biosciences Incorporated, 3832 Bay Center Place, Hayward, California 94545, USA. [email protected]
PMID: 19231864 DOI: 10.1021/jm900012a
Abstract

Inhibition of the protein chaperone HSP90 is a promising new approach to Cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.