Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
1 mg
5 mg
10 mg
1 mM
2.0055 mL
10.0273 mL
20.0545 mL
5 mM
0.4011 mL
2.0055 mL
4.0109 mL
10 mM
0.2005 mL
1.0027 mL
2.0055 mL
50 mM
0.0401 mL
0.2005 mL
0.4011 mL
Description
GDC-0152 is a potent antagonist of -BIR3, -BIR3, -BIR3 and -BIR3 with of 28 nM, 14 nM, 17 nM and 43 nM in cell-free assays, respectively; less affinity shown to cIAP1-BIR2 and cIAP2-BIR2. Phase 1.
GDC-0152 can block protein−protein interactions that involve IAP proteins and pro-apoptotic molecules. Using transiently transfected HEK293T cells, GDC-0152 is shown to disrupt XIAP binding to partially processed caspase-9 and to disrupt the association of ML-IAP, cIAP1, and cIAP2 with Smac. In melanoma SK-MEL28 cells, the endogenous association of ML-IAP and Smac is effectively also abolished by GDC-0152. GDC-0152 lead to a decrease in cell viability in the MDA-MB-231 breast cancer cell line, while having no effect on normal human mammary epithelial cells (HMEC). GDC-0152 is found to activate caspases 3 and 7 in a dose- and time-dependent manner. GDC-0152 is shown to induce rapid degradation of cIAP1 in A2058 melanoma cells. It effectively induces degradation of cIAP1 at concentrations as low as 10 nM, consistent with its affinity for cIAP1.
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 of 53.7 μM and AUC of 203.5 h•μM.
