TR-107

TR-107 is a potent, small-molecule activator of the mitochondrial protease ClpP (caseinolytic peptidase proteolytic subunit) developed by Madera Therapeutics for the treatment of cancer. It represents a new generation of ClpP activators with significantly higher potency than the related compound ONC201. TR-107 works by hyperactivating ClpP, which leads to the targeted degradation of mitochondrial proteins essential for oxidative phosphorylation (OXPHOS) and the TCA cycle. This disruption of mitochondrial metabolism results in growth inhibition and cell death in various cancer types, including triple-negative breast cancer (TNBC) and colorectal cancer. Preclinical data indicate that TR-107 has excellent oral bioavailability and pharmacokinetic properties, demonstrating tumor volume reduction and extended survival in xenograft models.