Comparative Study
doi: 10.1016/j.bmcl.2005.12.029.
Epub 2006 Jan 10.
Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase
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- PMID: 16406782
- DOI: 10.1016/j.bmcl.2005.12.029
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Comparative Study
Brequinar derivatives and species-specific drug design for dihydroorotate dehydrogenase
Bioorg Med Chem Lett.
.
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.
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