Synergistic effects have been observed with venetoclax in combination with direct Mcl-1 inhibition.122 This has led to combination studies with AZD5991 (Mcl-1 inhibitor) and venetoclax, which have shown efficacy in vivo, and authors demonstrated the combination could overcome therapy resistance.97 In a study of Mcl-1 inhibitor AMG 176, in combination with other approved AML therapies, authors found that the combination of AMG 176 and venetoclax worked synergistically and completely reduced tumor burden in mice.99 As mentioned above, MIK665/S64315 is a highly selective Mcl-1 inhibitor. The gene discussed is MCL1; the disease is acute myeloid leukemia.