Dynamic Ir(III) Photosensors for the Major Human Drug-Metabolizing Enzyme Cytochrome P450 3A4.

ABSTRACT: Probing the activity of cytochrome P450 3A4 (CYP3A4) is critical for monitoring the metabolism of pharmaceuticals and identifying drug-drug interactions. A library of Ir(III) probes that detect occupancy of the CYP3A4 active site were synthesized and characterized. These probes show selectivity for CYP3A4 inhibition, low cellular toxicity, K_d values as low as 9 nM, and are highly emissive with lifetimes up to 3.8 μs in cell growth media under aerobic conditions. These long emission lifetimes allow for time-resolved gating to distinguish probe from background autofluorescence from growth media and live cells. X-ray crystallographic analysis revealed structure-activity relationships and the preference or indifference of CYP3A4 toward resolved stereoisomers. Ir(III)-based pr

SUBMITTER: Denison M 

PROVIDER: S-EPMC10268476 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature