AZD 5991 is an inhibitor of myeloid cell leukemia-1 (Mcl-1; IC50 = 0.72 nM).1 It is selective for Mcl-1 over Bcl-2, Bcl-xL, Bcl-W, and Bfl-1 (IC50s = 20, 36, 49, and 24 ?M, respectively). AZD 5991 decreases the viability of MV4-11 acute myeloid leukemia (AML) and MOLP-8 multiple myeloma (MM) cells with EC50 values of 24 and 33 nM, respectively. It disrupts formation of the Mcl-1-Bak complex and induces apoptosis in MOLP-8 cells when used at a concentration of 500 nM. AZD 5991 induces complete tumor regression in MV4-11 and MOLP-8 mouse xenograft models when administered at a single dose of 100 mg/kg.
1.Tron, A.E., Belmonte, M.A., Adam, A., et al.Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemiaNat. Commun.9(1)5341(2018)