TR-107 (TR107) is a highly potent, selective and orally bioavailable small-molecule activator of the mitochondrial protease ClpP with EC50 of 140 nM, binds to purified ClpP with Kd value of 180 nM in surface plasmon resonance (SPR) measurement.
TR-107 dose‐dependent increases ClpP activity, inhibits breast cancer cell MDA‐MB‐231 and SUM159 growth (IC50=23 and 12 nM) in a ClpP‐dependent manner, without a significant increase in apoptosis.
TR-107 showed significantly enhanced potency of cell growth inhibition in the MDA‐MB‐231 and SUM159 cell models compared with ONC201 and ONC206.
TR‐107 (100 nM, 6-24 h) induces time‐ and dose‐dependent reduction of multiple mitochondrial proteins (TUFM and TFAM, aconitase (ACO2) and isocitrate dehydrogenase (IDH2), and succinate dehydrogenase A (SDHA) and complex I subunit NDUFS3).
TR‐107 reduces mitochondrial metabolic functions and inhibits OXPHOS in MDA‐MB‐231 cells.
TR‐107 (4-8 mg/kg, p.o.) prevents tumor growth in MDA‐MB‐231 xenograft model.