Table 3.

Relationship between pharmacodynamic biomarkers and TGI in the SW620 xenograft model

Dose of AZD5438 (mg/kg)Maximum % TGI*% Inhibition of pRb pSer249/pThr252 phosphorylation at 16 h after dose,AZD5438 tumor concentration in μg/g (μmol/L/g)AZD5438 plasma concentration in μg/mL (μmol/L/mL)
10075821.35 (0.0029)0.7 (0.0015)
5058490.4 (0.0009)1.04 (0.0022)
2532120.14 (0.0003)0.14 (0.0003)
  • *SW620 xenografts were established and then treated with vehicle alone or AZD5438 (once a day, orally) for 3 wk; maximum %TGI values, representing n = 10 per treatment group, were calculated as described in Materials and Methods.

  • Data generated 16 h after a single dose oral of AZD5438 (n = 3 treatment group).

  • Phospho-RbS249/T252 percentage inhibition calculated versus vehicle-dosed control.