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Details on Person Dihydroorotate dehydrogenase (DHODH) is the fourth, and rate...
| Class:Id | Summation:9708732 |
|---|---|
| _displayName | Dihydroorotate dehydrogenase (DHODH) is the fourth, and rate... |
| _timestamp | 2020-12-01 14:04:11 |
| created | [InstanceEdit:9708748] Jassal, Bijay, 2020-12-01 |
| modified | [InstanceEdit:9708844] Jassal, Bijay, 2020-12-01 |
| text | Dihydroorotate dehydrogenase (DHODH) is the fourth, and rate-limiting enzyme in the de novo pyrimidine nucleosides biosynthetic pathway. DHODH's expression is selectively upregulated in proliferating and activated lymphocytes, making it a target susceptible to pharmacological inhibition in activated immune cells. Inhibition of DHODH causes a reduction in the available pyrimidine pool, which leads to metabolic stress and apoptosis in highly activated cells. DHODH inhibitors are used clinically to treat autoimmune diseases such as rheumatoid arthritis (Davis et al. 1996, Breedveld & Dayer 2000) and multiple sclerosis (Palmer 2010). Novel potent inhibitors of human DHODH (S312, S416, vidofludimus and brequinar), as well as the existing drugs leflunomide and teriflunomide, all possess dual action of antiviral and immuno-regulation against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. These drugs may have clinical potentials to cure SARS-CoV-2 or other RNA viruses (Xiong et al. 2020, Coelho & Oliveira 2020, Hu et al. 2020, Maghzi et al. 2020). Brequinar has entered Phase 1/2 clinical evaluation in COVID-19 patients (NCT04425252). |
| (summation) | [Reaction:9708759] DHODH:FMN binds DHODH inhibitors [Homo sapiens] |
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