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. Here, BCL2 is linked to acute myeloid leukemia.