MCL1 and acute myeloid leukemia: AZD5991 is a macrocyclic molecule that directly binds to Mcl-1 with high affinity and is specific to Mcl-1 over other Bcl-2 family proteins.97 Upon binding to Mcl-1, AZD5991 promotes the release of Bak from the Mcl-1/Bak complex and rapidly initiates intrinsic apoptosis (Fig. 2b).97 Cytotoxicity of AZD5991 was shown to be highest in hematologic malignancies and more specifically in AML.