TRO40303 / Roche - LARVOL DELTA

DINCH Exposure Contributes to Osteoarthritis Pathogenesis via TSPO-Mediated Chondrotoxicity: Evidence from In Silico Prediction to Experimental Validation. (PubMed, Chem Biol Interact) - "Moreover, TRO-40303, as a TSPO-specific inhibitor, can effectively reverse TSPO upregulation-induced mitochondrial stress and chondrocyte senescence, thereby restoring the ECM metabolic balance in cartilage. Overall, this study elucidated the molecular mechanism by which DINCH exposure induced chondrotoxicity through TSPO targeting to drive OA development, providing new targets and theoretical foundations for the early diagnosis and intervention of environment-related OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • CAPN2 • STAT6

Pharmacology of mitochondrial permeability transition pore inhibitors. (PubMed, Drug Dev Res) - "However, clinical trials of cyclosporin A and TRO40303 have not provided a clear answer to the question of the effectiveness of mPTP inhibitors in patients with acute myocardial infarction. This article presents an analysis of possible approaches for the pharmacological regulation of mPTP during reperfusion injury of the heart."

Journal • Acute Coronary Syndrome • Cardiovascular • Immunology • Myocardial Infarction • Reperfusion Injury

Reperfusion-induced mitochondrial dysfunction in the porcine heart is reduced by TRO40303 in the area at risk predominantly through preservation of outer mitochondrial membrane intactness (ESC 2013) - Presentation time: 3 Sep, 14:00 - 18:00; Abstract# P5530; "...mitochondria in both the ischemic core area and the area at risk undergo significant alterations in respiratory function following ischemia-reperfusion injury consistent with both inner and outer mitochondrial membrane permeabilization which can be inhibited by hypothermia initiated prior to occlusion. Administration of TRO40303 prior to reperfusion appears to reduce reperfusion-induced mitochondrial dysfunction in the area at risk mainly by preserving outer membrane intactness and limiting CytC release."

Preclinical • Reperfusion Injury

Translational issues for mitoprotective agents as adjunct to reperfusion therapy in patients with ST-segment elevation myocardial infarction. (PubMed, J Cell Mol Med) - "We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI-9803, MTP131 and TRO 40303. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co-medication into account may be of paramount importance during the design of pre-clinical and clinical studies testing mitoprotective drugs."

Clinical • Journal • Review