title: On dihydroorotate dehydrogenases and their inhibitors and uses.
abstract: Proper nucleosides availability is crucial for the proliferation of living entities (eukaryotic cells, parasites, bacteria, and virus). Accordingly, the uses of inhibitors of the de novo nucleosides biosynthetic pathways have been investigated in the past. In the following we have focused on dihydroorotate dehydrogenase (DHODH), the fourth enzyme in the de novo pyrimidine nucleosides biosynthetic pathway. We first described the different types of enzyme in terms of sequence, structure, and biochemistry, including the reported bioassays. In a second part, the series of inhibitors of this enzyme along with a description of their potential or actual uses were reviewed. These inhibitors are indeed used in medicine to treat autoimmune diseases such as rheumatoid arthritis or multiple sclerosis (leflunomide and teriflunomide) and have been investigated in treatments of cancer, virus, and parasite infections (i.e., malaria) as well as in crop science.
authors: Institut Pasteur, Unité de Chimie et Biocatalyse, Département de Biologie Structurale et Chimie, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors: Hélène
authors: H
authors: Munier-Lehmann
authors: Pierre-Olivier
authors: PO
authors: Vidalain
authors: Frédéric
authors: F
authors: Tangy
authors: Yves L
authors: YL
authors: Janin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology; D003044:Coccidia / Q000201:enzymology; D003049:Coccidiostats / Q000627:therapeutic use; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics
chemical_list: D003049:Coccidiostats; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D044925:Oxidoreductases Acting on CH-CH Group Donors