S55746 (C09-1044-445)

InformationS55746 (S 055746,BCL201) is a novel, orally activeBCL-2specific inhibitor (Ki = 1.3 nM) with poor affinity for BCL-XL and no significant binding to MCL-1, BFL-1 (BCL2A1/A1). The selectivity of S55746 for BCL-2 versus BCL-XL ranges from ~70 to 400 folds.TargetsBcl-2 (Cell-free assay) 1.3 nM(Ki)In vitroS55746 occupies the hydrophobic groove of BCL-2. In a panel of hematological cell lines, S55746 induces hallmarks of apoptosis including externalization of phosphatidylserine, caspase-3 activation and PARP cleavage. S55746 potently induces RS4;11 cell killing after 72 h of treatment with an IC50 of 71.6 nM and exhibits a much weaker activity in H146 (IC50 = 1.7 μM), a BCL-XL-dependent cell line, which expresses a low level of BCL-2 and high level of BCL-XL. It has no cytotoxic activity on BCL-XL-dependent cells, such as platelets.In vivoS55746 administered by oral route daily in mice demonstrates robust anti-tumor efficacy in two hematological xenograft models (RS4;11 and Toledo models) with no weight lost and no change in behavior.Cell Research(from reference)Cell lines：RS4;11 cells Concentrations：0.01, 0.03, 0.1, 0.3, 1 μM Incubation Time：2 hours. Specifications and Purity: 98%. Molecular Formula: C43H42N4O6. Molecular Weight: 710.82. PubChem CID: 71654876. Isomeric SMILES: C1CCN2C(=C(C=C2C3=CC4=C(C=C3C(=O)N5CC6=CC=CC=C6C[C@H]5CN7CCOCC7)OCO4)C(=O)N(C8=CC=CC=C8)C9=CC=C(C=C9)O)C1.