20.500.12556/DiRROS-29102 Thiopurine S-methyltransferase – An important intersection of drug-drug interactions in thiopurine treatment Understanding the molecular mechanisms of medicines is crucial for developing novel drugs, for repurposing existing medicines, and for predicting toxicities. Thiopurine S-methyltransferase (TPMT) serves as an exemplary case in personalized medicine, as its activity is influenced by genetic variants, co-factors, substrates, and inhibitors, which lead to diverse outcomes in thiopurine therapy. This comprehensive review explores the role of TPMT in drug-drug interactions by investigating its interactions with co-factors, substrates, and inhibitors. We focus on the principal interactions of TPMT with clinically relevant inhibitors, and add to this information with molecular docking analyses for the substrate and co-factor binding sites of TPMT. Notably, methotrexate and sulfasalazine emerged as the top-ranked compounds with favorable docking scores for the co-factor binding site, while furosemide is presented as the highest ranked inhibitor for the substrate binding site. Furthermore, we highlight the chemical and structural properties governing ligand binding to TPMT. We support the molecular characteristics by using a summary of clinical implications. Examining the molecular interactions between substrates or inhibitors and TPMT not only addresses therapeutic consequences, but also reveals potential novel indications of interacting compounds. These insights are also invaluable for identifying endogenous ligands and enhancing our understanding of TPMT’s biological function. thiopurine S-methyltransferase drug-drug interactions thiopurines treatment outcome molecular docking methotrexate allopurinol tiopurin S-metiltransferaza interakcije med zdravili tiopurini izid zdravljenja molekularno združevanje metotreksat alopurinol true false true Angleški jezik Slovenski jezik Neznano 2026-04-21 09:54:44 2026-04-21 09:54:45 2026-04-22 04:04:09 0000-00-00 00:00:00 2025 0 0 19 str. [article no.] 117893 Vol. 184 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61-027.552:615 0753-3322 10.1016/j.biopha.2025.117893 225569283 RAZ_Urbancic_Dunja_2025.pdf RAZ_Urbancic_Dunja_2025.pdf 1 E83B86037ED591783D0AD339F8EC07D5 e3aaaac8dcd88e31cb26021194a57d8a0bc9e918b8259236080eaaa867ef94c7 94d563f1-3d57-11f1-a343-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43481 https://www.sciencedirect.com/science/article/pii/S0753332225000873 1 5eb41d83-3d57-11f1-a343-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43480 Univerzitetni klinični center Ljubljana 0 0 0