TY 51469 / Toa Eiyo - LARVOL DELTA

Beneficial Effects of Chymase Inhibition on Cardiac Diastolic Function and Remodeling Induced by Chronic Angiotensin II Stimulation. (PubMed, Int J Mol Sci) - "TY-51469 effectively suppressed these molecular changes and improved both cardiac structure and diastolic dysfunction, despite continued Ang II exposure. These results suggest that chymase promotes cardiac remodeling and dysfunction not only through Ang II generation but also by activating profibrotic and matrix-degrading factors, such as TGF-β1 and MMP-2."

Journal • Cardiovascular • Fibrosis • Immunology • MMP2 • TGFB1

Chymase Inhibition Attenuates Kidney Fibrosis in a Chronic Mouse Model of Renal Ischemia-Reperfusion Injury. (PubMed, Int J Mol Sci) - "However, treatment with TY-51469 significantly suppressed fibrosis formation, along with the inhibition of renal chymase and TGF-β1 expression. These findings suggest that chymase inhibition may be a potential therapeutic strategy for preventing the transition from AKI to CKD by reducing fibrosis."

Journal • Preclinical • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • Renal Disease • Reperfusion Injury • TGFB1

Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model. (PubMed, J Am Heart Assoc) - "Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi...Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY-51469) inhibited mMCP-4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo...Conclusions This study identified a major role for mMCP-4, a granule-localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Pulmonary Embolism • Respiratory Diseases • Thrombosis • Venous Thromboembolism

Sheltered in Stromal Tissue Cells, Trypanosoma cruzi Orchestrates Inflammatory Neovascularization via Activation of the Mast Cell Chymase Pathway. (PubMed, Pathogens) - "A classification algorithm showed that benznidazole (>24 h) blunted angiogenesis (7 dpi) in the HCP. Unbiased proteomics (3 dpi) combined to pharmacological targeting of chymase with two inhibitors (chymostatin and TY-51469) linked T. cruzi-induced neovascularization (7 dpi) to the proangiogenic activity of chymase, a serine protease stored in secretory granules from mast cells."

Journal • Immunology • Infectious Disease • Inflammation • IFNG • IL1B

Chymase as a Novel Therapeutic Target in Acute Pancreatitis. (PubMed, Int J Mol Sci) - "The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis."

Journal • Gastrointestinal Cancer • Hepatology • Immunology • Inflammation • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor • TNFA

Mast cell degranulation increases mouse Mast Cell Protease 4-dependent vasopressor responses to big endothelin-1 but not Angiotensin I. (PubMed, J Pharmacol Exp Ther) - "Significance Statement The current work demonstrates a significant role for mast cell stability in the cardiovascular pharmacology of big ET-1 but not Ang I in the murine systemic circulation. This study also demonstrate for the first time that an ACE-resistant Ang I analogue is susceptible to chymase-dependent activation in the mouse model."

Journal • Anesthesia • Cardiovascular • EDN1

Mechanism of Albuminuria Reduction by Chymase Inhibition in Diabetic Mice. (PubMed, Int J Mol Sci) - "Furthermore, the expression of nephrin, which is a podocyte-specific protein, was significantly reduced in the placebo-treated group, but it was restored in the TY-51469-treated group. These findings demonstrated that chymase inhibition reduced albuminuria via attenuation of podocyte injury by oxidative stress."

Journal • Preclinical • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • TNFA