Chemistry:Brequinar
 | |
| Clinical data | |
|---|---|
| Trade names | Brequinar |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C23H15F2NO2 |
| Molar mass | 375.4 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
Brequinar (DuP-785) is a drug that acts as a potent and selective inhibitor of the enzyme dihydroorotate dehydrogenase. It blocks synthesis of pyrimidine based nucleotides in the body and so inhibits cell growth. Brequinar was invented by DuPont Pharmaceuticals in the 1980s.[1] In 2001, Bristol-Myers Squibb acquired DuPont, and in 2017, Clear Creek Bio acquired the rights to brequinar from BMS.[2]
Brequinar has been investigated as an immunosuppressant for preventing rejection after organ transplant and also as an anti-cancer drug, but was not accepted for medical use in either application largely due to its narrow therapeutic dose range and severe side effects when dosed inappropriately.[3][4] It has been researched both as part of a potential combination therapy for some cancers,[5][6] or alternatively as an antiparasitic,[7] or antiviral drug.[8][9][10] Clear Creek Bio is currently developing brequinar as a potential treatment for COVID-19.[11]
Inhibition of dihydroorotate dehydrogenase activity by brequinar may represent an efficient approach to the elimination of undifferentiated cells for safe PSC‐derived differentiated cells based therapies.[12]
See also
- Leflunomide - Clinically used DHODH inhibitor
- Methotrexate - the most widely used pyrimidine synthesis inhibitor
References
- ↑ "Activity of a novel 4-quinolinecarboxylic acid, NSC 368390 [6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl-4-quinolinecarb oxylic acid sodium salt, against experimental tumors"]. Cancer Research 45 (11 Pt 1): 5563–5568. November 1985. PMID 4053030. https://pubmed.ncbi.nlm.nih.gov/4053030.
- ↑ "Bristol Myers Squibb Company History Timeline". May 3, 2022. https://www.bms.com/about-us/our-company/history-timeline.html.
- ↑ "Brequinar sodium". Pediatric Nephrology 9 Suppl: S52-5. 1995. doi:10.1007/bf00867685. PMID 7492488.
- ↑ "Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor". Nucleosides, Nucleotides & Nucleic Acids 37 (12): 666–678. 2018. doi:10.1080/15257770.2018.1508692. PMID 30663496.
- ↑ "Recent developments in the medicinal chemistry and therapeutic potential of dihydroorotate dehydrogenase (DHODH) inhibitors". Mini Reviews in Medicinal Chemistry 11 (12): 1039–55. October 2011. doi:10.2174/138955711797247707. PMID 21861807.
- ↑ "Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer". Pharmacology & Therapeutics 195: 111–131. March 2019. doi:10.1016/j.pharmthera.2018.10.012. PMID 30347213.
- ↑ "Dihydroorotate dehydrogenase inhibitors in anti-infective drug research". European Journal of Medicinal Chemistry 183: 111681. December 2019. doi:10.1016/j.ejmech.2019.111681. PMID 31557612.
- ↑ "Antiviral activity of brequinar against foot-and-mouth disease virus infection in vitro and in vivo". Biomedicine & Pharmacotherapy 116: 108982. August 2019. doi:10.1016/j.biopha.2019.108982. PMID 31146110.
- ↑ "Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine". Viruses 11 (10): 964. October 2019. doi:10.3390/v11100964. PMID 31635418.
- ↑ "Identification and characterization of novel compounds with broad spectrum antiviral activity against influenza A and B viruses". Journal of Virology 94 (7). January 2020. doi:10.1128/JVI.02149-19. PMID 31941776.
- ↑ "Clear Creek Bio Doses First Patient in Phase 2 Outpatient Study of Brequinar to Treat COVID-19". November 20, 2020. https://clearcreekbio.com/clear-creek-bio-doses-first-patient-in-phase-2-outpatient-study-of-brequinar-to-treat-covid-19.
- ↑ "Selective eradication of pluripotent stem cells by inhibiting DHODH activity". Stem Cells 39 (1): 33–42. October 2021. doi:10.1002/stem.3290. PMID 33038285.
 |  |
