ArticlePharmacology research & perspectives2022
Characterization of TR-107, a novel chemical activator of the human mitochondrial protease ClpP.
Article in Pharmacology research & perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Small molecule activators of the mitochondrial protease ClpP induce senescence in triple-negative breast cancer cells and sensitize cells to the Bcl-2 inhibitor venetoclax.Cell death & disease · 2026Article
- TUFM: a central regulator in mitochondrial quality control and beyond.Cell death discovery · 2026Review
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- The multifaceted roles of mitochondria and their therapeutic transformation: a new perspective on triple-negative breast cancer treatment.Frontiers in oncology · 2026Article
- The role of dordaviprone in the multidisciplinary management of diffuse midline glioma.Surgical neurology international · 2026Review
- Small Molecule Activators of the Mitochondrial Protease ClpP Induce Senescence in Triple-Negative Breast Cancer Cells and Sensitize Cells to the Bcl-2 Inhibitor Venetoclax.Research square · 2025Article
- Targeting the Mitochondrial Protease ClpP for Anticancer Therapy.Journal of medicinal chemistry · 2025Article
- Recent advances in the design of small molecules targeting human ClpP.Future medicinal chemistry · 2025Review
- Mitochondrial Protease ClpP: Cancer Marker and Drug Target.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- Dose Optimization of ClpP Agonists Using an In Vitro Microfluidic Perfusion Platform and In Silico Pharmacokinetic-Pharmacodynamic Modeling.The AAPS journal · 2025Article
- Targeting mitochondrial ClpP: structural insights and therapeutic potential of ClpP agonists in cancer therapy.Oncology reviews · 2025Review
- ZK53 enhances tumor cell susceptibility to ferroptosis via ClpP-mediated mitochondrial dysfunction.Frontiers in oncology · 2025Article
- Discovery of CLPP-1071 as an Exceptionally Potent and Orally Efficacious Human ClpP Activator with Strong In Vivo Antitumor Activity.Journal of medicinal chemistry · 2024Article
- TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells.Molecular cancer therapeutics · 2024Article
- Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.Molecular therapy. Oncology · 2024Article
- A review of current therapeutics targeting the mitochondrial protease ClpP in diffuse midline glioma, H3 K27-altered.Neuro-oncology · 2024Review
- TR-57 Treatment of SUM159 Cells Induces Mitochondrial Dysfunction without Affecting Membrane Potential.International journal of molecular sciences · 2024Article
- TUFM in health and disease: exploring its multifaceted roles.Frontiers in immunology · 2024Review
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
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 also reduced specific mitochondrial proteins, including OXPHOS and TCA cycle components, in a time-, dose-, and ClpP-dependent manner. Seahorse XF analysis and glucose deprivation experiments confirmed the inactivation of OXPHOS and increased dependence on glycolysis following TR-107 exposure. The pharmacokinetic properties of TR-107 were compared with other known ClpP activators including ONC201 and ONC212. TR-107 displayed excellent exposure and serum t
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.