VU661013

VU661013 is a potent and selective small molecule inhibitor of Myeloid Cell Leukemia-1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family that is frequently overexpressed in various cancers to evade programmed cell death. Developed by researchers at Vanderbilt University, VU661013 binds with high affinity to the BH3-binding groove of Mcl-1, thereby displacing pro-apoptotic proteins like BIM and BAK. This action facilitates mitochondrial outer membrane permeabilization (MOMP) and triggers the intrinsic apoptotic pathway. Preclinical studies have demonstrated its efficacy in hematologic malignancies, including acute myeloid leukemia (AML) and multiple myeloma (MM), where it has shown potential to overcome resistance to other therapies such as venetoclax or bortezomib.