Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase.

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Hurt DE, Sutton AE, Clardy J

Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase.

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1610-5. Epub 2006 Jan 10.

PubMed ID

16406782 [ View in PubMed

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Abstract

Therapeutic agents brequinar sodium and leflunomide (Arava) work by binding in a hydrophobic tunnel formed by a highly variable N-terminus of family 2 dihydroorotate dehydrogenase (DHODH). The X-ray crystallographic structure of an analog of brequinar bound to human DHODH was determined. In silico screening of a library of compounds suggested another subset of brequinar analogs that do not inhibit human DHODH as potentially effective inhibitors of Plasmodium falciparum DHODH.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
5-Carbamoyl-1,1':4',1''-terphenyl-3-carboxylic acid	Dihydroorotate dehydrogenase (quinone), mitochondrial	Ki (nM)	2800	8	22	Details