BDA-366

BDA-366 is an antagonist of the BH4 domain of the anti-apoptotic protein Bcl-2 (K_i = 3.3 nM).¹ It is selective for Bcl-2 over Bcl-xL, Mcl-1, A1/Bfl-1, and Bcl-2 lacking the BH4 domain (K_is = >500, >500, >500, and 654.8 nM, respectively) but does bind to BH1-, BH2-, or BH3 domain-deficient Bcl-2 (K_is = 12.4, 7.6, and 23.4 nM, respectively). However, BDA-366 (10 µM) induces Bax activation in HT cells, which lack endogenous Bcl-2, and in HT cells overexpressing Bcl-2, indicating a context-specific Bcl-2-independent mechanism of cell death.² BDA-366 is cytotoxic against a panel of non-small cell lung cancer (NSCLC) and SCLC cell lines (IC₅₀s = 0.2-1.73 µM).¹ It also reduces tumor growth and induces tumoral caspase-3 activation in an H460 lung cancer mouse xenograft model when administered at doses of 10, 20, and 30 mg/kg.²

WARNING This product is not for human or veterinary use.

1. Han, B., Park, D., Li, R., et al. Small-molecule Bcl2 BH₄ antagonist for lung cancer therapy. Cancer Cell 27(6), 852-863 (2015).

2. Vervloessem, T., Sasi, B.K., Xerxa, E., et al. BDA-366, a putative Bcl-2 BH₄ domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models. Cell Death Dis. 11(9), 769 (2020).