On dihydroorotate dehydrogenases and their inhibitors and uses.

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Munier-Lehmann H, Vidalain PO, Tangy F, Janin YL

On dihydroorotate dehydrogenases and their inhibitors and uses.

J Med Chem. 2013 Apr 25;56(8):3148-67. doi: 10.1021/jm301848w. Epub 2013 Mar 20.

PubMed ID

23452331 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Atovaquone	Dihydroorotate dehydrogenase (quinone), mitochondrial	IC 50 (nM)	14500	N/A	N/A	Details
Brequinar	Dihydroorotate dehydrogenase (quinone), mitochondrial	IC 50 (nM)	6	N/A	N/A	Details
Brequinar	Dihydroorotate dehydrogenase (quinone), mitochondrial	IC 50 (nM)	10	N/A	N/A	Details