GDC-0152 disrupts protein−protein interactions involving IAP proteins and pro-apoptotic molecules. In HEK293T cells transiently transfected, GDC-0152 disrupts XIAP binding to partially processed caspase-9 and the association of ML-IAP, cIAP1, and cIAP2 with Smac. In SK-MEL28 melanoma cells, GDC-0152 effectively abolishes the endogenous association of ML-IAP and Smac. It reduces cell viability in MDA-MB-231 breast cancer cells but not in normal human mammary epithelial cells (HMEC). GDC-0152 activates caspases 3 and 7 in a dose- and time-dependent manner. Additionally, GDC-0152 induces rapid degradation of cIAP1 in A2058 melanoma cells, with effective degradation observed at concentrations as low as 10 nM, consistent with its affinity for cIAP1 [1].
体内研究
GDC-0152 exhibits moderate predicted hepatic clearance based on metabolic stability assays conducted using human liver microsomes. Plasma−protein binding of GDC-0152 is moderate and consistent across species, including mice (88−91%), rats (89−91%), dogs (81−90%), monkeys (76−85%), and humans (75−83%) over the investigated concentration range (0.1−100 μM); rabbits show higher plasma−protein binding (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. Pharmacokinetic parameters for GDC-0152 include a C max of 53.7 μM and AUC of 203.5 h·μM [1].
体外研究
GDC-0152 disrupts protein−protein interactions involving IAP proteins and pro-apoptotic molecules. In HEK293T cells transiently transfected, GDC-0152 disrupts XIAP binding to partially processed caspase-9 and the association of ML-IAP, cIAP1, and cIAP2 with Smac. In SK-MEL28 melanoma cells, GDC-0152 effectively abolishes the endogenous association of ML-IAP and Smac. It reduces cell viability in MDA-MB-231 breast cancer cells but not in normal human mammary epithelial cells (HMEC). GDC-0152 activates caspases 3 and 7 in a dose- and time-dependent manner. Additionally, GDC-0152 induces rapid degradation of cIAP1 in A2058 melanoma cells, with effective degradation observed at concentrations as low as 10 nM, consistent with its affinity for cIAP1 [1].
GDC-0152 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HIV-infected resting memory CD4+ T cells (HIV-T CM)
10 nM
24 hours
Induced cell death in HIV-T CM without increasing virus production
Cell Host Microbe. 2018 Nov 14;24(5):689-702.e7.
C8B4 cells
1 µM
72 hours
GDC-0152 promoted the anti-tumoral function of C8B4 cells via caspase-3 pro-inflammatory cleavage and NF-κB activation, and inhibited the growth of tumoroids.
Cell Death Dis. 2024 Sep 15;15(9):676.
Human glioblastoma-derived CD45+ cells
1 µM
72 hours
GDC-0152 treatment altered the morphology of CD45+ cells, increasing their area and affecting cytokine secretion, indicating functional changes.
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