Article
Discovery of a highly selective CYP3A4 inhibitor suitable for reaction phenotyping studies and differentiation of CYP3A4 and CYP3A5.
Drug metabolism and disposition: the biological fate of chemicals - 1 Sept 2012
Li Xiaohai, Song Xinyi, Kamenecka Theodore M, Cameron Michael D
Abstract excerpt
Current molecular tools lack the ability to differentiate the activity of CYP3A4 and CYP3A5 in biological samples such as human liver microsomes. Kinetic experiments and the CYP3A4 crystal structure indicate that the active sites of both enzymes are large and flexible, and have more than one binding subsite within the active site. 1-(4-Imidazopyridinyl-7phenyl)-3-(4'-cyanobiphenyl) urea (SR-9186) was optimized...
Topics
- Cytochrome P-450 CYP3A
- Cytochrome P-450 CYP3A Inhibitors
- Dose-Response Relationship, Drug
- Drug Discovery
- Enzyme Inhibitors
- Half-Life
- Humans
- Hydroxylation
- Imidazoles
- Ketoconazole
- Liver
- Microsomes, Liver
- Midazolam