A-1331852 is a high affinity BH3 mimetic Ligand of BCL protein BCL-XL, binding to the target potently and selectively with a Ki value of 600-fold selectivity), BCL-W (Ki = 4 nM, >400-fold selectivity), and MCL-1 (Ki = 142 nM, >14000-fold selectivity). It selectively disrupts BCL-XL–BIM complex and induces the hallmarks of apoptosis in BCL-XL–dependent Molt-4 cells with IC50 values in the low nM range without any measurable effects on MEF cells lacking BAK or BAX. Orally administered A-1331852 demonstrates antitumor efficacy in the Molt-4 xenograft model, inducing tumor regressions as a single agent. It significantly inhibits tumor growth given ether as a single agent, or combined with docetaxel in seven subcutaneous xenograft models of solid tumors, including breast cancer, NSCLC, and ovarian cancer. A-1331852, together with A-1155463 (Axon 3957), represent the first-in-class small molecule BCL-XL selective inhibitors achieving clear-on-target in vivo activity with high potency and selectivity.

KEYWORDS: A-1331852 | Supplier | BCL-XL selective inhibitor | A1331852 | A 1331852 | CT-A133 | CAS [1430844-80-6] | Non Selective | Bcl | Inhibitor | Proteins