BDA-366

BDA-366 is an antagonist of the BH4 domain of the anti-apoptotic protein Bcl-2 (Ki = 3.3 nM). It is selective for Bcl-2 over Bcl-xL, Mcl-1, A1/Bfl-1, and Bcl-2 lacking the BH4 domain (Kis = >500, >500, >500, and 654.8 nM, respectively) but does bind to BH1-, BH2-, or BH3 domain-deficient Bcl-2 (Kis = 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. BDA-366 is cytotoxic against a panel of non-small cell lung cancer (NSCLC) and SCLC cell lines (IC50s = 0.2-1.73 µM). 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.Formal Name: 1-[[(2S)-3-(diethylamino)-2-hydroxypropyl]amino]-4-[[(2S)-2-oxiranylmethyl]amino]-9,10-anthracenedione. CAS Number: 1909226-00-1. Molecular Formula: C24H29N3O4. Formula Weight: 423.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: 2 mg/ml. lambdamax: 255, 590, 635 nm. SMILES: CCN(CC)C[C@@H](O)CNC(C=C1)=C(C(C2=CC=CC=C2C3=O)=O)C3=C1NC[C@H]4CO4. InChi Code: InChI=1S/C24H29N3O4/c1-3-27(4-2)13-15(28)11-25-19-9-10-20(26-12-16-14-31-16)22-21(19)23(29)17-7-5-6-8-18(17)24(22)30/h5-10,15-16,25-26,28H,3-4,11-14H2,1-2H3/t15-,16-/m0/s1. InChi Key: JYOOEVFJWLBLKF-HOTGVXAUSA-N.