Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2.

Abstract

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.

• Authors: Pierre Lafite, Sylvie Dijols, Didier Buisson, Anne-Christine Macherey, Darryl C Zeldin, Patrick M Dansette, Daniel Mansuy
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 10 Pg. 2777-80 (May 15 2006) ISSN: 0960-894X [Print] England
• PMID: 16495056 (Publication Type: Journal Article)

Chemical References

• CYP2J2 protein, human
• Cytochrome P-450 Enzyme Inhibitors
• Enzyme Inhibitors
• Cytochrome P-450 Enzyme System
• Oxygenases
• Cytochrome P-450 CYP2J2

Topics

• Cytochrome P-450 CYP2J2
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Enzyme System (metabolism)
• Drug Design
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Humans
• Magnetic Resonance Spectroscopy
• Oxygenases (antagonists & inhibitors, metabolism)
• Substrate Specificity