TR57

TR57 (also known as TR-57) is a highly potent, second-generation small-molecule imipridone analog and mitochondrial caseinolytic protease P (ClpP) agonist developed by Madera Therapeutics. By binding to and hyperactivating ClpP, TR57 induces uncontrolled proteolysis of mitochondrial proteins, leading to respiratory chain dysfunction, depletion of mitochondrial DNA (mtDNA), and activation of the integrated stress response (ISR) and mitochondrial unfolded protein response (UPRmt). TR57 has demonstrated significant preclinical efficacy as a cytostatic and cytotoxic agent in various cancer models, including triple-negative breast cancer (TNBC) and chronic lymphocytic leukemia (CLL), where it has shown synergistic activity in combination with the Bcl-2 inhibitor venetoclax.

Other names

ClpP agonist TR-57