title: Human dihydroorotate dehydrogenase inhibitors, a novel approach for the treatment of autoimmune and inflammatory diseases.
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.
authors.affiliation: 4SC AG, Martinsried, Germany. johann.leban@4SC.com
authors.forename: Johann
authors.initials: J
authors.lastname: Leban
authors.forename: Daniel
authors.initials: D
authors.lastname: Vitt
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy*; D000090722:Dihydroorotate Dehydrogenase; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000077339:Leflunomide; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000077339:Leflunomide