GDC-0152 is a potent inhibitor of IAPs.

XIAP BIR2:112 nM(Ki), XIAP BIR3:28 nM(Ki), CIAP2-BIR3:43 nM(Ki), MLXBIR3SG:14 nM(Ki), CIAP1-BIR3:17 nM(Ki)

GDC-0152能够阻断涉及IAP蛋白和促凋亡分子的蛋白质-蛋白质相互作用。通过使用瞬时转染的HEK293T细胞，展示了GDC-0152打断XIAP与部分处理的caspase-9的结合，并中断了ML-IAP、cIAP1和cIAP2与Smac的关联。GDC-0152同样有效地废除了黑色素瘤SK-MEL28细胞中ML-IAP与Smac的内源性关联。在MDA-MB-231乳腺癌细胞系中，GDC-0152导致细胞活力下降，而对正常人乳腺上皮细胞（HMEC）无影响。GDC-0152发现能以剂量和时间依赖的方式激活caspases 3和7。在A2058黑色素瘤细胞中，GDC-0152显示出能快速降解cIAP1。它在低至10 nM的浓度下有效地促进cIAP1的降解，与其对cIAP1的亲和力一致。

GDC-0152基于使用人类肝微粒体进行的代谢稳定性分析，预计具有中等程度的肝脏清除率。GDC-0152的血浆-蛋白结合率为中等，且在不同物种间相似，包括小鼠（88−91%）、大鼠（89−91%）、狗（81−90%）、猴子（76−85%）和人类（75−83%），在研究的浓度范围内（0.1−100 μM）；而在兔子中观察到更高的血浆-蛋白结合率（95−96%）。GDC-0152不倾向于特别分布到红细胞，所有测试物种中的血液-血浆分配比率为0.6到1.1。GDC-0152的药代动力学达到C max为53.7 μM，AUC为203.5 h·μM。[1]

Fluorescence polarization-based competition assay: Inhibition constants ( Ki ) for the antagonists are determined by addition of the IAP protein constructs to wells containing serial dilutions of the antagonists or the peptide AVPW, and the Hid-FAM probe or AVP-diPhe-FAM probe, as appropriate, in the polarization buffer. Samples are read after a 30-minute incubation. Fluorescence polarization values are plotted as a function of the antagonist concentration, and the IC50 values are obtained by fitting the data to a 4-parameter equation using software. Ki values for the antagonists are determined from the IC50 valued.

MDA-MB-231 breast carcinoma cells and HMECs are treated with the indicated concentrations of GDC-0152. Cell death is assessed using the CellTiter-Glo luminescent cell viability assay 72 h following the start of treatment.(Only for Reference)