title: Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus.
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.
authors.affiliation: Kosan Biosciences Incorporated, 3832 Bay Center Place, Hayward, California 94545, USA. menzella@ibr.gov.ar
authors.forename: Hugo G
authors.initials: HG
authors.lastname: Menzella
authors.forename: Thomas-Toan
authors.initials: TT
authors.lastname: Tran
authors.forename: John R
authors.initials: JR
authors.lastname: Carney
authors.forename: Janice
authors.initials: J
authors.lastname: Lau-Wee
authors.forename: Jorge
authors.initials: J
authors.lastname: Galazzo
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Reeves
authors.forename: Christopher
authors.initials: C
authors.lastname: Carreras
authors.forename: Sophie
authors.initials: S
authors.lastname: Mukadam
authors.forename: Sara
authors.initials: S
authors.lastname: Eng
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhong
authors.forename: Pieter B M W M
authors.initials: PB
authors.lastname: Timmermans
authors.forename: Sumati
authors.initials: S
authors.lastname: Murli
authors.forename: Gary W
authors.initials: GW
authors.lastname: Ashley
mesh_terms: D002151:Calorimetry; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D005818:Genetic Engineering; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D017828:Rifabutin / Q000494:pharmacology*; D013302:Streptomyces / Q000235:genetics*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D017828:Rifabutin