TR-107 / Madera Therap - LARVOL DELTA

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. (PubMed, Res Sq) - "We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines...By contrast, cells treated with the cell cycle inhibitor and senescence inducer, abemaciclib rapidly regained p-Rb and Myc expression and cell proliferation following washout...Combining a ClpP agonist with a PARP inhibitor (olaparib) produced an additive effect. In summary, we show that ClpP activators stably induce an irreversible senescence in a ClpP-dependent manner that synergizes with venetoclax in TNBC cells."

IO biomarker • Journal • Breast Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer • CHEK2 • LMNB1 • MYC • TP53BP1

Integrated multi-omics study identifies ursolic acid as a novel therapeutic agent targeting the TNF-α/TAK1/IKKβ/NF-κB axis in hepatic sinusoidal obstruction syndrome (ASH 2025) - "The busulfan-cyclophosphamide (BUCY)conditioning regimen induces endothelial injury, thereby initiating a thromboinflammatory cascade.While TNF-α/NF-κB signaling is implicated in this process, its precise role and therapeutic targeting in SOSremain undefined...In vitro: Primary rat HSECswere treated with BUCY ± UA, NF-κB was overexpressed (OE-p65 plasmid) or inhibited (BAY 11-7082).Apoptosis (Annexin V/PI flow cytometry), ROS (DCFH-DA), mRNA (qPCR), and protein (WB) levels of TNF-α/NF-κB pathway components and antioxidants were measured...MD simulations revealed stable binding of BUCYmetabolites (e.g., acrolein, ΔG=-8.2 kcal/mol) and UA to TNF-α (Tyr59/Trp107, ΔG=-9.3 kcal/mol)... TNF-α/NF-κB signaling critically drives BUCY-induced HSEC injury and SOS. UA, a first-in-classnatural TNF-α inhibitor, binds TNF-α with high affinity, thereby blocking downstream TAK1/IKKβ/NF-κBactivation. This mechanism suppresses endothelial inflammation, oxidative stress, and..."

IO biomarker • Bone Marrow Transplantation • Hepatology • Inflammation • ANXA5 • BAX • BCL2 • CASP3 • FASLG • ICAM1 • IL1B • IL6 • MMP9 • NFKBIA • RELA • TNFA • VCAM1

TR-107 MODULATES THE INFLAMMATORY PHENOTYPE OF PANCREATIC CANCER AND MAINTAINS EFFICACY AGAINST ORGANOIDS IN HYPOXIC CONDITIONS (DDW 2025) - "TR-107 maintains efficacy in PDAC cell lines and organoids in hypoxia. TR-107 treatment may modulate the hypoxic and/or inflammatory phenotype of PDAC, as evidenced by decreased HIF-1α levels and immune chemokine results of the inflammatory PCR array post-treatment. This alteration may ultimately translate to decreased tumor viability and sensitivity to chemotherapeutics."

Clinical • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • CLPP • CXCL10 • CXCL11 • HIF1A • TFAM

Combination of the ClpP agonist TR107 and the MCL1 inhibitor MIK665 enhances cytotoxicity in breast cancer cells [WITHDRAWN] (AACR 2025) - "Ongoing work involves testing the combination in vivo and investigating specific biomarkers that predict cell line sensitivity to the drug combination. In summary, we found strongly additive or synergistic therapeutic efficacy of a treatment combining TR-107 and MIK665 in multiple breast cancer cell lines."

IO biomarker • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Leukemia • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL2 • CLPP • ER • HER-2 • PGR