The 7th International Enzyme and Bioprocess Days (EBDays 2026)

The 7th International Enzyme and Bioprocess Days (EBDays 2026), Trabzon, Türkiye, 26 - 28 Ağustos 2026, ss.95, (Özet Bildiri)

Investigating the Effects of CYP2C9 Genetic Variants on Drug Recognition and Pharmacokinetic Profiles Using Computational Approaches

BERÇEM ALKAN, AYŞE MINA ARSLANBAŞ, HALIL İBRAHIM GÜLER

Karadeniz Technical University, Faculty of Science, Molecular Biology and Genetics, Trabzon, Türkiye

Pharmacogenetic variations in drug-metabolizing enzymes are among the major determinants of interindividual

differences in drug response. Cytochrome P450 2C9 (CYP2C9) is responsible for the metabolism of numerous clinically

important drugs, and genetic polymorphisms within this enzyme may significantly alter its catalytic activity and substrate

recognition. In this study, the effects of two common CYP2C9 variants, CYP2C92 (R144C) and CYP2C93 (I359L), on drug

binding were investigated using structure-based computational approaches. Three clinically relevant CYP2C9 substrates,

S-warfarin, phenytoin, and diclofenac, were selected as model ligands. Three-dimensional structures of the variant

proteins were generated through homology modeling, and molecular docking analyses were performed against both wild-

type and variant CYP2C9 enzymes. Binding affinities and interaction patterns were comparatively evaluated to assess the

influence of genetic variations on ligand recognition. In addition, ADMET analyses were conducted using SwissADME and

pkCSM platforms to investigate the pharmacokinetic and toxicological profiles of the selected compounds. The results

demonstrated that pharmacogenetic variations altered both binding affinities and interaction networks of the

investigated ligands. The CYP2C93 variant consistently exhibited weaker binding affinities compared with the wild-type

enzyme, whereas ligand-dependent effects were observed for the CYP2C92 variant. ADMET predictions revealed

favorable pharmacokinetic characteristics and safety profiles consistent with previous reports. These findings suggest that

CYP2C9 polymorphisms may contribute to variability in drug metabolism and therapeutic outcomes. Overall, this study

highlights the importance of integrating pharmacogenetic information into personalized medicine strategies and provides

molecular-level insights into CYP2C9-mediated drug interactions.

Keywords: CYP2C9, pharmacogenetics, molecular docking, drug metabolism, ADMET