BCL2 and lung carcinoma: BDA-366 was the first molecule reported to directly bind to the BH4 domain of BCL2 and thus to serve as a BH4 antagonist, capable of killing lung cancer and MM cells.399,400 The mechanism for this cell death effect was attributed to its ability to convert BCL2 into a pro-apoptotic protein by triggering the exposure of its BH3 domain, thereby resulting in BAX/BAK activation.401 As such, cancer cells with high levels of BCL2 were more susceptible to BDA-366.