AZD4320 is a BH3 mimetic and dual Bcl-2/Bcl-XL inhibitor with IC50 of <1 nM.
AZD4320 induces caspase-3 cleavage and cell death in both Bcl-2-driven (SuDHL4, GI50 <50 nM) and Bcl-xL-driven (SuDHL8, GI50 <50 nM) diffuse large B-cell lymphoma (DLBCL) cell lines.
AZD4320 treatment results in complete and sustained (>24 days) tumor regressions in a mouse RS4;11 acute lymphocytic leukemia xenograft model (20 mg/kg, i.v.).
1. Ashkenazi A, et al. Nat Rev Drug Discov. 2017 Apr;16(4):273-284.
2. Hennessy, E. J. et al. Discovery of potent inhibitors of the antiapoptotic proteins Bcl-2 and Bcl-xL, resulting in the identification of a clinical candidate for the treatment of cancer (AZD4320). ACS Medicinal Chemistry annual meeting 2015.
