Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes.

ABSTRACT: PF74 and 11L, as potent modulators of the HIV-1 capsid protein, have been demonstrated to act at both early and late stages in the HIV-1 life cycle. However, their clearance is high in human liver microsomes (HLMs). The main goal of this study was to clarify the metabolism of PF74 and 11L in HLMs, and provide guidance for future structural optimization. To accomplish this, the phase-I metabolites of PF74 and 11L, resulting from in vitro incubation with HLMs, were investigated via ultra-performance liquid chromatography-ultraviolet-high-resolution mass spectrometry (UPLC-UV-HRMS). The results show that 17 phase-I metabolites were putatively annotated for PF74, whereas 16 phase-I metabolites were found for 11L. The main metabolic pathwa

SUBMITTER: Xu S 

PROVIDER: S-EPMC9412436 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature