Human dihydroorotate dehydrogenase inhibitors, a novel approach for the treatment of autoimmune and inflammatory diseases

Arzneimittelforschung. 2011;61(1):66-72. doi: 10.1055/s-0031-1296169.

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.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Arthritis, Rheumatoid / drug therapy
  • Autoimmune Diseases / drug therapy*
  • Dihydroorotate Dehydrogenase
  • Drug Design
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Inflammation / drug therapy*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
  • Randomized Controlled Trials as Topic
  • Structure-Activity Relationship

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Dihydroorotate Dehydrogenase
  • Enzyme Inhibitors
  • Isoxazoles
  • Oxidoreductases Acting on CH-CH Group Donors
  • Leflunomide