title: Discovery of covalent inhibitors for MIF tautomerase via cocrystal structures with phantom hits from virtual screening.
abstract: Biochemical and X-ray crystallographic studies confirmed that hydroxyquinoline derivatives identified by virtual screening were actually covalent inhibitors of the MIF tautomerase. Adducts were formed by N-alkylation of the Pro-1 at the catalytic site with a loss of an amino group of the inhibitor.
authors.affiliation: Discovery Research, sanofi-aventis, Bridgewater, NJ 08807, USA. Larry.Mclean@sanofi-aventis.com
authors.forename: Larry R
authors.initials: LR
authors.lastname: McLean
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lukasczyk
authors.forename: Yong-Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Zuoning
authors.initials: Z
authors.lastname: Han
authors.forename: Joy
authors.initials: J
authors.lastname: Prisco
authors.forename: Jeremy
authors.initials: J
authors.lastname: Fordham
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tsay
authors.forename: Stephan
authors.initials: S
authors.lastname: Reiling
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Vaz
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors*; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006912:Hydroxyquinolines; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases