BMS-665351 induces the expression of hCAR, not hPXR, and de novo protein synthesis is required for BMS-665351-induced CYP3A4 expression. Cultured HepG2, Huh7, and human primary hepatocytes from donors HL-16 and HL-17 were treated with RIF (10 μM), CITCO (1 μM), PB (1 mM), or BMS-665351 (1 and 5 μM) for 24 h. A to D, total RNA was collected, reverse-transcribed, and subjected to quantitative PCR for detecting hCAR (A and B) and hPXR (C and D) expression levels. E, in separate experiments, HPHs from donors HL-44 and HL-53 were exposed to CHX (5 μg/ml), Act.D (1 μM), or vehicle 1 h before BMS-665351 treatment (5 μM, 24 h) for quantitative PCR detection of CYP3A4 mRNA expression. All quantitative PCR data are expressed as mean ± S.D. (n = 3). *, P < 0.05; **, P < 0.01.