Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures.
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.
McLean
Larry R
LR
Discovery Research, Sanofi-aventis, Bridgewater, NJ 08807, USA. Larry.Mclean@sanofi-aventis.com
Zhang
Ying
Y
Degnen
William
W
Peppard
Jane
J
Cabel
Dasha
D
Zou
Chao
C
Tsay
Joseph T
JT
Subramaniam
Arun
A
Vaz
Roy J
RJ
Li
Yi
Y
D018360:Crystallography, X-Ray; D000090722:Dihydroorotate Dehydrogenase; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors*
D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D044925:Oxidoreductases Acting on CH-CH Group Donors