Biotransformation of 6-Methoxy-3-(3,4,5-trimethoxy-benzoyl)-1H- indole (BPR0L075), a Novel Antimicrotubule Agent, by Mouse, Rat, Dog, and Human Liver Microsomes

is a novel synthetic indole compound with microtubule binding activity. Incubation of BPR0L075 with mouse, rat, dog, and human liver microsomes in the presence of NADPH resulted in the forma-tion of six metabolites. Liquid chromatography-tandem mass spectrometry and comparison with the synthetic reference stan-dards identified two metabolites (M1 and M5) as the products derived from hydroxylation on the indole moiety of the molecule. M3 was also identified as a product derived from hydroxylation, but the structure of this metabolite was not identified because of the lack of a reference standard. M2, M4, and M6 were identified as the products derived from O-demethylation. M2, 6-desmethyl-BPR0L075, was the major metabolite formed by the liver micro-somes of the four species. No qualitative species difference in the metabolism of BPR0L075 was observed. There was quantitative species difference in the metabolism of BPR0L075 among the fou