TR-107

TR-107 is an activator of the caseinolytic protease P (ClpP; EC₅₀ = 140 nM).¹ It reduces the proliferation of MDA-MB-231 and SUM159 breast cancer cells (IC₅₀ = 23 and 12 nM, respectively). TR-107 (10 or 100 nM) decreases the levels of elongation factor Tu (EF-Tu), mitochondrial transcription factor A (TFAM), isocitrate dehydrogenase (IDH), heat shock protein 60, (Hsp60), and mitochondrial complex II, also known as succinate dehydrogenase, in a ClpP-dependent manner in MDA-MB-231 and SUM159 cells. It reduces oxygen consumption rate, basal mitochondrial respiration, ATP production-linked oxygen consumption, maximal respiration, spare respiratory capacity, and extracellular acidification in a ClpP-dependent manner in MDA-MB-231 cells when used at a concentration of 50 nM. TR-107 decreases tumor volume in an MDA-MB-231 mouse xenograft model.

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1. Fennell, E.M.J., Aponte-Collazo, L.J., Wynn, J.D., et al. Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP. Pharmacol. Res. Perspect. 10(4), e00993 (2022).