Fig. 8: BMAL1 promotes ccRCC xenograft growth and sensitivity to PT2399 in vivo.

A–F Volume of xenograft tumors grown from 786O cells implanted in flanks of female NIH-III Nude mice treated with 10 mg/kg of PT2399 unless otherwise indicated or vehicle control three times weekly by oral gavage between ZT0 and ZT2 (A–E) or at ZT0 (open symbols) or ZT12 (filled symbols) (F). In (A–D) dark and light green symbols represent xenografts grown from 786O cells expressing wildtype (dark green) or D144A mutant (light green) BMAL1; filled and open symbols represent tumors in mice treated with vehicle control or with PT2399, respectively. In (E, F) black and red symbols represent xenografts grown in mice treated with vehicle control or with PT2399, respectively. **P < 0.01, ****P < 0.0001 by simple linear regression. In (A, E), P values represent comparison to 786O and to 30 mg/kg, respectively. In (A–E), n = 5 animals per group. In (F), n = 3 for the group treated with PT2399 at ZT12 because two mice died before the completion of the study. Data represent mean ± s.e.m. Source data are provided as a Source Data file.