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

MENZELLA H.G. (CORRESPONDING); TRAN T.; CARNEY J.; LAU-WEE J.; GALAZZO J.; REEVES C.; CARRERAS C.; MUKADAM S.; TIMMERMANS P.; MURLI S.; ASHLEY G.

JOURNAL OF MEDICINAL CHEMISTRY

AMER CHEMICAL SOC

Año: 2009 vol. 26 p. 1518 - 1521

0022-2623

Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe a robust method for the preparation of potent non-benzoquinone ansamycins.  One of these analogs, 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.