Dr. Reyhane Chamani, , , ,
Volume 11, Issue 4 (2-2025)
Abstract
Deactivation of drugs by enzymes, especially UDP-glucuronosyltransferases (UGT), is a reasons for resistance. The aim of this study was to investigate the interaction of UGT1A3, UGT1A1 and UGT2B7 enzymes with tyrosine kinase inhibitors. The structure of enzymes was made by homology modeling method and the structure of 300 tyrosine kinase inhibitors was obtained from Pubchem database. Molecular docking simulation was performed by PyRx 0.8 software and the complexes were sorted based on the most negative binding energy and zero RMSD and the amino acids involved in the binding were analyzed. In total, forty-five drugs were introduced as possible substrates of these three enzymes. The results showed that the binding site of these drugs were to the amino acids of the active site of the enzymes and the binding energy of the ligands to UGT1A1 was more negative than the other two enzymes. It can be suggested that the possible glucuronidation of these inhibitors by UGT enzymes can lead to two important events: first, their rapid removal from the blood circulation and creating drug resistance, and second, preventing bilirubin glucuronidation and increasing serum bilirubin level. Therefore, laboratory investigation of the relationship between these inhibitors and UGT enzymes can be necessary.
