Jh. Kelly et Nl. Sussman, A fluorescent cell-based assay for cytochrome P-450 isozyme 1A2 induction and inhibition, J BIOMOL SC, 5(4), 2000, pp. 249-253
High throughput lead optimization requires simple, homogeneous cell-based a
ssays capable of defining the drug-like properties of first-round screening
hits. Induction and inhibition of the Phase I drug-metabolizing enzymes ar
e central to this process. We report here an assay for induction and inhibi
tion of cytochrome P-450 (CYP) isozyme 1A2 that meets these requirements. I
t utilizes HepG2/C3A, a human liver cell line, and ethoxyresorufin. Using m
ethylcholanthrene, CYP1A2 can be induced dramatically, and it is inhibited
by furafylline, a mechanism-based inhibitor of this enzyme.