| Naslov: | Thiopurine S-methyltransferase – An important intersection of drug-drug interactions in thiopurine treatment |
|---|
| Avtorji: | ID Urbančič, Dunja (Avtor)
ID Jukič, Marko (Avtor)
ID Šmid, Alenka (Avtor)
ID Gobec, Stanislav (Avtor)
ID Jazbec, Janez (Avtor)
ID Mlinarič-Raščan, Irena (Avtor) |
|---|
| Datoteke: |  PDF - Predstavitvena datoteka, prenos (7,95 MB)
MD5: E83B86037ED591783D0AD339F8EC07D5
 URL - Izvorni URL, za dostop obiščite https://www.sciencedirect.com/science/article/pii/S0753332225000873
|
|---|
| Jezik: | Angleški jezik |
|---|
| Tipologija: | 1.02 - Pregledni znanstveni članek |
|---|
| Organizacija: |  UKC LJ - Univerzitetni klinični center Ljubljana
|
|---|
| Povzetek: | 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. |
|---|
| Ključne besede: | thiopurine S-methyltransferase, drug-drug interactions, thiopurines, treatment outcome, molecular docking, methotrexate, allopurinol |
|---|
| Status publikacije: | Objavljeno |
|---|
| Verzija publikacije: | Objavljena publikacija |
|---|
| Leto izida: | 2025 |
|---|
| Št. strani: | 19 str. |
|---|
| Številčenje: | Vol. 184, [article no.] 117893 |
|---|
| PID: | 20.500.12556/DiRROS-29102  |
|---|
| UDK: | 61-027.552:615 |
|---|
| ISSN pri članku: | 0753-3322 |
|---|
| DOI: | 10.1016/j.biopha.2025.117893 |
|---|
| COBISS.SI-ID: | 225569283 |
|---|
| Datum objave v DiRROS: | 21.04.2026 |
|---|
| Število ogledov: | 226 |
|---|
| Število prenosov: | 226 |
|---|
| Metapodatki: |    |
|---|
|
:
|
Kopiraj citat |
|---|
| | | | Objavi na: |  |
|---|
Postavite miškin kazalec na naslov za izpis povzetka. Klik na naslov izpiše
podrobnosti ali sproži prenos. |
