2. Academic Validation
  3. Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

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

Affiliation

  • 1 Kosan Biosciences Incorporated, 3832 Bay Center Place, Hayward, California 94545, USA. menzella@ibr.gov.ar
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.

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