Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures

Larry R McLean; Ying Zhang; William Degnen; Jane Peppard; Dasha Cabel; Chao Zou; Joseph T Tsay; Arun Subramaniam; Roy J Vaz; Yi Li

doi:10.1016/j.bmcl.2010.01.115

Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures

Bioorg Med Chem Lett. 2010 Mar 15;20(6):1981-4. doi: 10.1016/j.bmcl.2010.01.115. Epub 2010 Jan 25.

Authors

Larry R McLean¹, Ying Zhang, William Degnen, Jane Peppard, Dasha Cabel, Chao Zou, Joseph T Tsay, Arun Subramaniam, Roy J Vaz, Yi Li

Affiliation

¹ Discovery Research, Sanofi-aventis, Bridgewater, NJ 08807, USA. Larry.Mclean@sanofi-aventis.com

PMID: 20153645
DOI: 10.1016/j.bmcl.2010.01.115

Abstract

Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Crystallography, X-Ray
Dihydroorotate Dehydrogenase
Drug Discovery
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Models, Molecular
Molecular Structure
Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*

Substances

Dihydroorotate Dehydrogenase
Enzyme Inhibitors
Oxidoreductases Acting on CH-CH Group Donors