A-1155463 is a proteolytically stable, cell-permeable and high affinity BH3 mimetic Ligand of BCL protein BCL-XL, binding to the target potently and selectively with a Ki value of 7000-fold selectivity), BCL-W (Ki = 8 nM, >800-fold selectivity), and MCL-1 (Ki >444nM, >40000-fold selectivity). A-1155463, together with A-1331852 (Axon 3972), represent the first-in-class small molecule BCL-XL selective inhibitors achieving clear-on-target in vivo activity with high potency and selectivity. In living cells, A-1155463, as anticipated, experts an effort to disrupt the tight-binding BCL-XL-BIM, but not BCL-2–BIM, complexes, killing BCL-XL–dependent Molt-4 cells (EC50=70nM) without measurable cytotoxicity against BCL-2–dependent RS4, inducing the hallmarks of intrinsic apoptosis.

KEYWORDS: A-1155463 dihydrochloride | Supplier | BCL-XL selective inhibitor | A1155463 | A 1155463 | CT-A115 | CAS [N.A.] | [1235034-55-5] | Non Selective | Bcl | Inhibitor | Proteins