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

Kosan Biosciences Incorporated, 3832 Bay Center Place, Hayward, California 94545, USA.
Journal of Medicinal Chemistry (Impact Factor: 5.61). 03/2009; 52(6):1518-21. DOI: 10.1021/jm900012a
Source: PubMed

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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