Compound 77

Compound 77 is a small molecule inhibitor of the anti-apoptotic protein Myeloid cell leukemia 1 (Mcl-1), a member of the Bcl-2 family. Developed by researchers at the University of Michigan and collaborating institutions, it was identified as a potent analogue of a lead compound (Compound 59) discovered through high-throughput screening. Compound 77 functions as a BH3 mimetic, binding to the BH3 domain of Mcl-1 and preventing its interaction with pro-apoptotic proteins. This antagonism induces cytochrome c release and triggers apoptosis in a Bax/Bak-dependent manner. Preclinical studies have demonstrated its efficacy in inhibiting the growth of Mcl-1-overexpressing cancer cells, including pancreatic cancer and melanoma models.