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Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype. ClpP is a component of the ClpXP protein complex localized in the mitochondrial matrix. Modifiers of ClpP activity have demonstrated anti-cancer properties. TR-107 is a potent chemical activator of the human mitochondrial protease ClpP, with excellent potency, specificity and drug-like properties. TR‐107 shows ClpP‐dependent growth inhibition in the low nanomolar range that is equipotent to Paclitaxel in TNBC cell models.  The pharmacokinetic properties of TR‐107 were compared with other known ClpP activators including ONC201 and ONC212. TR‐107 displayed excellent exposure and serum t1/2 after oral administration. Pharmacokinetic analysis were evaluated for pharmacokinetic properties in ICR mice by Medicilon.

Reference

Emily M J Fennell, et al. Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP. Pharmacol Res Perspect. 2022 Aug;10(4):e00993. doi: 10.1002/prp2.993.