Biotransformation of Geldanamycin and 17-Allylamino-17-Demethoxygeldanamycin by Human Liver Microsomes: Reductive versus Oxidative Metabolism and Implications

• Published in: Drug metabolism and disposition Vol. 35; no. 1; pp. 21 - 29
• Main Authors: Lang, Wensheng, Caldwell, Gary W, Li, Jian, Leo, Gregory C, Jones, William J, Masucci, John A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.01.2007
• Subjects: Antibiotics, Antineoplastic - metabolism; Benzoquinones - metabolism; Biological and medical sciences; Biotransformation; Cell Hypoxia; HSP90 Heat-Shock Proteins - antagonists & inhibitors; Humans; Lactams, Macrocyclic - metabolism; Medical sciences; Microsomes, Liver - metabolism; NADPH-Ferrihemoprotein Reductase - metabolism; Oxidation-Reduction; Pharmacology. Drug treatments; Human; Digestive system; Biotransformation; Liver; Geldanamycin; Pharmacokinetics; Microsome; Metabolism; In vitro; Comparative study

Comparative metabolite profiling of geldanamycin and 17-allylamino-17-demethoxygeldanamycin (17AAG) using human liver microsomes in normoxia and hypoxia was conducted to understand their differential metabolic fates. Geldanamycin bearing a 17-methoxy group primarily underwent reductive metabolism, g...