GDC-0152

GDC-0152 is a potent antagonist of XIAP-BIR3, ML-IAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 28 nM, 14 nM, 17 nM and 43 nM, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1. (In Vivo) :GDC-0152 has moderate predicted hepatic clearance based on metabolic stability assays conducted using human liver microsomes. Plasma protein binding of GDC-0152 is moderate and comparable among mice (88 91%), rats (89 91%), dogs (81 90%), monkeys (76 85%), and humans (75 83%) over the range of concentrations investigated (0.1 100 μM) ; higher plasma protein binding is observed in rabbits (95 96%) . GDC-0152 does not preferentially distribute to red blood cells with blood plasma partition ratios ranging from 0.6 to 1.1 in all species tested. The pharmacokinetics for GDC-0152 is achieved with a C max of 53.7 μM and AUC of 203.5 h·μM.