Potency assay (cells):
In mouse FL5.12 cells that depend on BCL2 for survival in the absence of IL-3, venetoclax led to cell death. In comparable cells dependent upon BCL-XL, venetoclax had an EC50=261 nM. In ALL cells, venetoclax had an EC50 (cell death) in BCL2-dependent cells (RS4;11)=8 nM and in BCL-XL-dependent cells (H146)=4,260 nM. In a mammalian cell 2-hybrid assay, venetoclax disrupted BCL2-BIM complex (EC50=3 nM) but BCL-XL-BIM complex (EC50=2.2 uM). Venetoclax had no impact on Bak/Bax double knockout mouse embryonic fibroblasts.
Target engagement assay (cells):