title: Isolation and structure of homotemsirolimuses A, B, and C.
abstract: Homotemsirolimuses A, B, and C (2a, 2b, 2c) were found to be minor components of a temsirolimus preparation made from rapamycin. These three temsirolimus analogues are derived from the corresponding rapamycin analogues, homorapamycins A, B, and C (1a, 1b, 1c) produced by the strain Streptomyces hygroscopicus. The structures of homotemsirolimuses A, B, and C were determined by spectroscopic methods. These compounds were tested for mTOR kinase inhibition and in two proliferation assays using LNCap prostate and MDA468 breast cancer cells. The results suggested that the mTOR inhibition and antiproliferation potencies for 2a, 2b, and 2c are comparable to those of rapamycin (1) and temsirolimus (2).
authors: Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. fangming.kong@pfizer.com
authors: Fangming
authors: F
authors: Kong
authors: Tianmin
authors: T
authors: Zhu
authors: Ker
authors: K
authors: Yu
authors: Thomas G
authors: TG
authors: Pagano
authors: Parimal
authors: P
authors: Desai
authors: Galen
authors: G
authors: Radebaugh
authors: Mahdi
authors: M
authors: Fawzi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C122078:FKBP9 protein, human; C558961:homotemsirolimuse A; C558962:homotemsirolimuse B; C558963:homotemsirolimuse C; C401859:temsirolimus; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus