Structural highlights
Disease
[PYRD_HUMAN] Defects in DHODH are the cause of postaxial acrofacial dysostosis (POADS) [MIM:263750]; also known as Miller syndrome. POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases.[1]
Function
[PYRD_HUMAN] Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
Publication Abstract from PubMed
The structure-activity relationships of a novel series of biaryl dihydroorotate dehydrogenase (DHODH) inhibitors related to teriflunomide are disclosed. These biaryl derivatives were the result of structure-based design and proved to be potent DHODH inhibitors which in addition showed good antiproliferative activities on peripheral blood mononuclear cells and good efficacies in vivo in the rat adjuvant-induced-arthritis model.
Biaryl analogues of teriflunomide as potent DHODH inhibitors.,Erra M, Moreno I, Sanahuja J, Andres M, Reinoso RF, Lozoya E, Pizcueta P, Godessart N, Castro-Palomino JC Bioorg Med Chem Lett. 2011 Dec 15;21(24):7268-72. Epub 2011 Oct 20. PMID:22078215[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010 Jan;42(1):30-5. doi: 10.1038/ng.499. Epub 2009 Nov 13. PMID:19915526 doi:10.1038/ng.499
- ↑ Erra M, Moreno I, Sanahuja J, Andres M, Reinoso RF, Lozoya E, Pizcueta P, Godessart N, Castro-Palomino JC. Biaryl analogues of teriflunomide as potent DHODH inhibitors. Bioorg Med Chem Lett. 2011 Dec 15;21(24):7268-72. Epub 2011 Oct 20. PMID:22078215 doi:http://dx.doi.org/10.1016/j.bmcl.2011.10.052
