Receptor tyrosine kinase (RTK) (RTK)

Receptor tyrosine kinases (RTKs) are a diverse group of high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. They play a critical role in the regulation of cell growth, differentiation, and survival by catalyzing the phosphorylation of tyrosine residues on themselves and downstream signaling proteins [Source: UniProt; StatPearls, Receptor Tyrosine Kinase]. In the context of the therapeutic agent nintedanib, the target specifically involves the Vascular Endothelial Growth Factor Receptors (VEGFR 1-3), Platelet-Derived Growth Factor Receptors (PDGFR alpha and beta), and Fibroblast Growth Factor Receptors (FGFR 1-3) [Source: FDA Label, Ofev, 2023]. These specific RTKs are central to the processes of angiogenesis and fibrogenesis, which are often pathologically activated in malignancies and chronic fibrosing lung diseases [Source: PubChem CID 135450548]. Nintedanib acts as a potent, competitive inhibitor of the adenosine triphosphate (ATP) binding site on the intracellular kinase domains of these receptors. By blocking these receptors, nintedanib inhibits the signaling pathways (such as Ras/MAPK and PI3K/Akt) that lead to the proliferation and migration of fibroblasts and endothelial cells. This mechanism effectively slows the progression of idiopathic pulmonary fibrosis (IPF) and inhibits tumor vascularization and growth in non-small cell lung cancer (NSCLC) [Source: NIH, DailyMed - Ofev].

Other names

RTKsProtein-tyrosine kinase receptorsVEGFRPDGFRFGFRVascular endothelial growth factor receptorPlatelet-derived growth factor receptorFibroblast growth factor receptorTriple angiokinase targets

Nintedanib acts as a competitive inhibitor of the adenosine triphosphate (ATP) binding site on the intracellular kinase domains of VEGFR, PDGFR, and FGFR, thereby blocking receptor autophosphorylation and inhibiting downstream signaling pathways such as MAPK and PI3K/Akt [Source: FDA Label, Ofev; StatPearls, Nintedanib].