Academic Journal
The Dihydroorotate Dehydrogenase Inhibitor Brequinar Is Synergistic with ENT1/2 Inhibitors
| Τίτλος: | The Dihydroorotate Dehydrogenase Inhibitor Brequinar Is Synergistic with ENT1/2 Inhibitors |
|---|---|
| Συγγραφείς: | Christine R. Cuthbertson, Hui Guo, Armita Kyani, Joseph T. Madak, Zahra Arabzada, Nouri Neamati |
| Πηγή: | ACS Pharmacology & Translational Science. 3:1242-1252 |
| Στοιχεία εκδότη: | American Chemical Society (ACS), 2020. |
| Έτος έκδοσης: | 2020 |
| Θεματικοί όροι: | 0301 basic medicine, 03 medical and health sciences, 0302 clinical medicine, 3. Good health |
| Περιγραφή: | The dihydroorotate dehydrogenase (DHODH) inhibitor brequinar failed all clinical trials for solid tumors. To investigate mechanisms to increase brequinar's efficacy, we employed a combination strategy to simultaneously inhibit the nucleotide salvage pathways. Brequinar is synergistic with the equilibrative nucleoside transporter (ENT) inhibitor dipyridamole, but not the concentrative nucleoside transporter inhibitor phlorizin. This synergy carries over to ENT1/2 inhibition, but not ENT4. Our previously described brequinar analogue 41 was also synergistic with dipyridamole as were the FDA-approved DHODH inhibitors leflunomide and teriflunomide but the latter required much higher concentrations than brequinar. Therefore, a combination of brequinar and ENT inhibitors presents a potential anti-cancer strategy in select tumors. |
| Τύπος εγγράφου: | Article Other literature type |
| Γλώσσα: | English |
| ISSN: | 2575-9108 |
| DOI: | 10.1021/acsptsci.0c00124 |
| Σύνδεσμος πρόσβασης: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737209 https://pubmed.ncbi.nlm.nih.gov/33344900 https://pubmed.ncbi.nlm.nih.gov/33344900/ https://pubs.acs.org/doi/10.1021/acsptsci.0c00124 https://pubs.acs.org/doi/full/10.1021/acsptsci.0c00124 https://www.ncbi.nlm.nih.gov/pubmed/33344900 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737209 |
| Rights: | STM Policy #29 |
| Αριθμός Καταχώρησης: | edsair.doi.dedup.....ee19d810692bf2992bfaed9304b0e420 |
| Βάση Δεδομένων: | OpenAIRE |
| ISSN: | 25759108 |
|---|---|
| DOI: | 10.1021/acsptsci.0c00124 |