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

…, J Lau-Wee, J Galazzo, CD Reeves…

Index: Menzella, Hugo G.; Tran, Thomas-Toan; Carney, John R.; Lau-Wee, Janice; Galazzo, Jorge; Reeves, Christopher D.; Carreras, Christopher; Mukadam, Sophie; Eng, Sara; Zhong, Ziyang; Timmermans, Pieter B. M. W. M.; Murli, Sumati; Ashley, Gary W. Journal of Medicinal Chemistry, 2009 , vol. 52, # 6 p. 1518 - 1521

Full Text: HTML

Citation Number: 26

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 ...