Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP.

ABSTRACT: We recently described the identification of a new class of small-molecule activators of the mitochondrial protease ClpP. These compounds synthesized by Madera Therapeutics showed increased potency of cancer growth inhibition over the related compound ONC201. In this study, we describe chemical optimization and characterization of the next generation of highly potent and selective small-molecule ClpP activators (TR compounds) and demonstrate their efficacy against breast cancer models in vitro and in vivo. We selected one compound (TR-107) with excellent potency, specificity, and drug-like properties for further evaluation. TR-107 showed ClpP-dependent growth inhibition in the low nanomolar range that was equipotent to paclitaxel in triple-negative breast cancer (TNBC) cell models. TR-107 a

SUBMITTER: Fennell EMJ 

PROVIDER: S-EPMC9354705 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature