Abstract
Dihydroorotate dehydrogenase (DHODH), a novel and recently discovered enzyme, is involved in the biosynthesis of uridine. Leflunomide (CAS 75706-12-6), a drug approved for the treatment of treat rheumatoid arthritis (RA), was identified as an inhibitor of DHODH. Structure based drug design using the leflunomide/DHODH X-ray structure yielded novel inhibitors with improved pharmacological properties. Such drug candidates are in clinical trials against various autoimmune diseases.
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Arthritis, Rheumatoid / drug therapy
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Autoimmune Diseases / drug therapy*
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Dihydroorotate Dehydrogenase
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Drug Design
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / therapeutic use*
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Humans
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Inflammation / drug therapy*
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Isoxazoles / chemistry
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Isoxazoles / pharmacology
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Isoxazoles / therapeutic use
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Leflunomide
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Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
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Randomized Controlled Trials as Topic
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Dihydroorotate Dehydrogenase
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Enzyme Inhibitors
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Isoxazoles
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Oxidoreductases Acting on CH-CH Group Donors
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Leflunomide