Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2.
The active site topology, substrate specificity, and biological roles of the human cytochrome P450 CYP2J2, which is mainly expressed in the cardiovascular system, are poorly known even though recent data suggest that it could be a novel biomarker and potential target for therapy of human cancer. This paper reports a first series of high-affinity, selective CYP2J2 inhibitors that are related to terfenadine, with K(i) values as low as 160nM, that should be useful tools to determine the biological roles of CYP2J2.
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Universite Paris 5 René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France.
Pierre
P
Lafite
Sylvie
S
Dijols
Didier
D
Buisson
Anne-Christine
AC
Macherey
Darryl C
DC
Zeldin
Patrick M
PM
Dansette
Daniel
D
Mansuy
D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010105:Oxygenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013379:Substrate Specificity
C000717350:CYP2J2 protein, human; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000090762:Cytochrome P-450 CYP2J2