ACD/Regioselectivity of Metabolism

Predict metabolic soft spots for metabolism by human liver microsomes and Cytochrome P450 enzymes from structure

The CYP Regioselectivity model is able to provide valuable insights into a compound's metabolic profile early in the drug discovery process when little or no experimental information is available, and labor intensive investigation of each compound in the screening process is prohibited by the large number of compounds involved. These predictions can help identify metabolic sites on new chemical entities; guide synthesis of compounds with improved metabolic properties; and help identify and elucidate likely metabolite structures. Predictions are provided for the main metabolic reactions mediated by the Human Liver Microsomes (HLM), and five individual major Cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2).

About the Model

Main Features

  • Predictions are based on probabilistic models, developed using GALAS (Global, Adjusted Locally According to Similarity) modeling methodology, for 5 most common metabolic reactions (N-dealkylation, O-dealkylation, aliphatic hydroxylation, aromatic hydroxylation, S-oxidation).
  • A quantitative estimate of prediction reliability is provided by Reliability Index (RI)—a number from 0 to 1 (0—poor reliability, 1—excellent reliability), indicating similarity of the current metabolic site to our internal training set, and consistency of model predictions for similar sites.

Data Sources
Peer-reviewed original articles with analytical identification of the metabolites observed after the incubation of compound with human liver microsomes or recombinant cytochrome P450 enzymes. In these compounds each carbon atom, with at least one hydrogen attached, produced a new data point that was considered positive if a metabolic reaction taking place at that site was experimentally observed, and negative otherwise).

Training set size: >900 compounds

Isoform No. of Data Points
CYP1A2 6464
CYP2C19 5474
CYP2C9 6645
CYP2D6 6708
CYP3A4 7728
Overall HLM data 8791

ACD/Labs Product Suites

The Percepta prediction modules are available as bundles to offer cost savings for multiple modules, and provide related modules as a package.

Other Products

ACD/Regioselectivity of Metabolism Model predictions are available as a browser-based thin client application on ACD/Percepta Portal; a thick client product (ACD/Percepta for the Desktop); and a batch calculator (ACD/Percepta Batch).