Potent Non-Benzoquinone Ansamycin Heat Shock Protein 90 Inhibitors from Genetic Engineering of Streptomyces hygroscopicus

ArticleinJournal of Medicinal Chemistry 52(6):1518-21 · March 2009with17 Reads
Impact Factor: 5.45 · DOI: 10.1021/jm900012a · Source: PubMed


    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.