a-1155463

A-1155463 is a highly potent and selective small molecule inhibitor of BCL-XL (BCL2-like 1), a member of the BCL-2 family of anti-apoptotic proteins[1][3][7][6]. It was discovered through fragment-based NMR screening and structure-based design as a tool for probing BCL-XL biology and as a lead for optimization[3][7]. A-1155463 binds BCL-XL with picomolar affinity and shows >1000-fold selectivity over BCL-2 and related proteins such as BCL-W and MCL-1[3]. The inhibitor induces apoptosis in BCL-XL-dependent tumor cells and demonstrates anti-tumor activity in models of small cell lung cancer and mantle cell lymphoma, especially when combined with Venetoclax (VEN), a BCL2 inhibitor[3][2][5][6][8]. Monotherapy produces reversible thrombocytopenia due to BCL-XL inhibition in platelets[3][1]. The molecule is used extensively in research to dissect BCL family dependencies and mechanisms of drug resistance[2][5][8]. A-1155463 served as the pharmacophore for the development of orally active analog A-1331852[4][7]. It is not approved for human use and remains a research tool molecule.

Other names

A-1155463A1155463A 11554631235034-55-5