Effects of BMS-665351 on PXR and CAR activation in transfected HepG2 cells and HPHs. A, B, C, E, F, and G, HepG2 cells were transfected with CYP3A4 (PXRE/XREM) reporter construct in the presence of hPXR (A), hCAR3 (B), or hCAR1+A (C) expression vectors or in the combination of CYP2B6-2.2kb reporter construct with hPXR (E), hCAR3 (F), or hCAR1+A (G) expression vectors. Transfected cells were then treated with BMS-665351 (1 and 5 μM) for 24 h. RIF (10 μM) and CITCO (1 μM) were used as positive controls for hPXR and hCAR, respectively. D and H, in separate experiments, human primary hepatocytes from donors HL-16 and HL-40 in 24-well Biocoat plates were transfected with CYP3A4 (PXRE/XREM) (D) or CYP2B6-2.2kb (H) reporter vector, followed by treatment of RIF (10 μM), CITCO (1 μM), PB (1 mM), and BMS-665351 (1 and 5 μM) for 24 h. Luciferase activities were determined and expressed relative to vehicle control. Data represent the mean ± S.D. (n = 3). **, P < 0.01.