What is the mechanism of action of Nintedanib?

Nintedanib(Nintedanib) is a small molecule kinase inhibitor used to treat pulmonary fibrosis, systemic sclerosis-related interstitial lung disease and non-small cell lung cancer (non-small cell lung cancer). Nintedanib(Nintedanib)What is its mechanism of action?

Nintedanib is a small molecule, competitive triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Many of these RTKs are associated with pulmonary fibrosis and tumor angiogenesis, and therefore nintedanib is indicated for the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-related interstitial lung disease. NintedanibSpecificity of inhibitionRTKsare platelet-derived growth factor(PDGFR) α and β, fibroblast growth factor receptor(FGFR) 1-3, vascular endothelial growth factor receptor(VEGFR) 1-3 and Fns-like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP binding pocket of these receptors and inhibits their activity, thereby blocking signaling cascades that lead to lung fibroblast proliferation and migration. Nintedanib also inhibits kinase signaling pathways in various cells within tumor tissue, including endothelial cells, pericytes, smooth muscle cells, and cells that contribute to angiogenesis, ultimately inhibiting cell proliferation and apoptosis of affected tumor cells. In addition to RTKinhibition, nintedanib also blocks the nRTKs Lck, Lyn and Src action. The contribution of inhibition of 8,9,5Lck and Lyn to nintedanib's therapeutic effect is unclear, but nintedanibinhibition of the Src pathway has been shown to reduce pulmonary fibrosis.

The absolute bioavailability of nintedanib is low, approximately4.7%, possibly due to extensive first-pass metabolism and P-The role of glycoprotein(P-gp) transporter. The maximum is reached after approximately 2 hours after oral administration in fasted patients and approximately 4 hours after oral administration in fed patients, independent of the food ingested. Taking nintedanib after a high-fat, high-calorie meal results in a Cmaximum of approximately 15% and an AUC increase of approximately 20%. Age, weight, and smoking status have been found to modifynintedanibexposure, but these effects are not sufficient to warrant a change in dosage. There are generic drugs in India, and each box costs about 400. If you want to get more high-quality information, you can contact Yaode, and Yaode will do its best to learn more about high-quality overseas drugs for you.