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Nintedanib - Brands
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 implicated in lung fibrosis and tumour angiogenesis, so nintedanib is therefore used in the treatment of proliferative diseases such as idiopathic pulmonary fibrosis, non-small cell lung cancer, and systemic sclerosis-associated interstitial lung disease. The specific RTKs that nintedanib inhibits are platelet-derived growth factor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR), and Fns-Like tyrosine kinase-3 (FLT3). Nintedanib binds to the ATP-binding pocket of these receptors and inhibits their activity, thereby blocking signalling cascades that result in the proliferation and migration of lung fibroblasts. Nintedanib also inhibits kinase signalling pathways in various cells within tumour tissues, including endothelial cells, pericytes, smooth muscle cells, and cells contributing to angiogenesis, culminating in an inhibition of cell proliferation and apoptosis of affected tumour cells.
In addition to RTK inhibition, nintedanib also prevents the actions of the nRTKs Lck, Lyn, and Src. The contribution of the inhibition of Lck and Lyn towards the therapeutic efficacy of nintedanib is unclear, but inhibition of the Src pathway by nintedanib has been shown to reduce lung fibrosis.
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