BAM7

BAM7 (BAX Activator Molecule 7) is a first-in-class small molecule that directly activates the pro-apoptotic protein BAX. It was identified through in silico structural similarity screening and competitive fluorescence polarization assays to target the BAX 'trigger site,' an allosteric pocket located at the N-terminal region of the protein. Engagement of this site by BAM7 induces a conformational change in BAX, converting it from an inactive cytosolic monomer into a lethal, oligomeric pore-forming protein that permeabilizes the mitochondrial outer membrane. This mechanism bypasses the requirement for upstream BH3-only proteins, allowing BAM7 to restore apoptosis in cancer cells that have developed resistance through the overexpression of anti-apoptotic BCL-2 family members. BAM7 served as the chemical lead for the development of more potent second-generation activators such as BAM38.

Other names

BAX activator molecule 7