Background

Cytochrome P450 (CYP) enzymes are membrane-bound hemeproteins that play a key role in metabolism of drugs and xenobiotics. Most drugs are mainly metabolized by cytochrome P450 (CYP450), which can lead to drug–drug interactions (DDI). Specifically, time-dependent inhibition (TDI) of CYP3A4 isoenzyme has been associated with clinically relevant DDI. To overcome potential DDI issues, high-throughput in vitro assays were established to assess the TDI of CYP3A4 during the discovery and lead optimization phases.

Benchmarking

The goal of this benchmark is to perform a single task, which is to have the best predictive model for CYP3A4 inactivation rate log_kobs.

Description of readout

• Readouts: log_kobs
• Bioassay readout: CYP3A4 inactivation rate

Molecule data resource:

Reference: https://pubs.acs.org/doi/10.1021/acs.chemrestox.3c00305

Train/test split

In this benchmark set, the train/test sets in the above paper are used.

Distribution of the train/test in the chemical space

Related links

The full curation and creation process is documented here.