Background:

CUDC-427 is a potent second-generation pan-selective IAP antagonist, used for treatment of various cancers.

GDC-0917 (0.1 nM-10 μM) induces reduction of cIAP1 levels in PBMCs in a concentration-dependent manner showing greater than 80% inhibition at concentrations greater than 0.1 µM (56.5 ng/mL)[1].

GDC-0917 (0.08-16.3 mg/kg) exhibits antitumor activity in a dose dependent manner in the MDA-MB-231-X1.1 Breast Cancer Xenograft, and GDC-0917 is well tolerated, with all dose groups experiencing a<11% decrease in mean body weight. GDC-0917 has low to moderate clearance in the mouse (12.0 mL/min/kg), rat (27.0 mL/min/kg), and dog (15.3 mL/min/kg), and high clearance in the monkey (67.6 mL/min/kg). Oral bioavailability is lowest in monkeys compared with other species[1].

[1]. Wong H, et al. Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist. Drug Metab Dispos. 2013 Dec;41(12):2104-13.