Kingsley, Laura J. published the artcileCombining Structure- and Ligand-Based Approaches to Improve Site of Metabolism Prediction in CYP2C9 Substrates, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome p450 substrate metabolism site prediction QSAR simulation.
Purpose: Predicting atoms in a potential drug compound that are susceptible to oxidation by cytochrome P 450 (CYP) enzymes is of great interest to the pharmaceutical community. We aimed to develop a computational approach combining ligand- and structure-based design principles to accurately predict sites of metabolism (SoMs) in a series of CYP2C9 substrates. Methods: We employed the reactivity model, SMARTCyp, ensemble docking, and pseudo-receptor modeling based on quant. structure-activity relationships (QSAR) to account for influences of both the inherent reactivity of each atom and the phys. structure of the CYP2C9 binding site. Results: We tested ligand-based prediction alone (i.e. SMARTCyp), structure-based prediction alone (i.e. AutoDock Vina docking), the linear combination of the SMARTCYP and docking scores, and finally a pseudo-receptor QSAR model based on the docked compounds in combination with SMARTCyp. We found that by using the latter combined approach we were able to accurately predict 88% and 96% of the true SoMs, within the top-1 and top-2 predictions, resp. Conclusions: We have outlined a novel combination approach for accurately predicting SoMs in CYP2C9 ligands. We believe that this method may be applied to other CYP2C9 ligands as well as to other CYP systems.
Pharmaceutical Research published new progress about Drug metabolism. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem