Receptor tyrosine kinases (VEGFR, PDGFR, and FGFR families) (VEGFR/PDGFR/FGFR)

This target group encompasses several families of receptor tyrosine kinases (RTKs), specifically the Vascular Endothelial Growth Factor Receptors (VEGFR1-3), Platelet-Derived Growth Factor Receptors (PDGFR-alpha/beta), and Fibroblast Growth Factor Receptors (FGFR1-4). These receptors are characterized by an extracellular ligand-binding domain and an intracellular tyrosine kinase domain, which are essential for mediating cellular responses to growth factors (UniProt: P17948, P09619, P11362). They play pivotal roles in physiological processes such as angiogenesis, lymphangiogenesis, and mesenchymal cell proliferation. In many cancers and fibrotic diseases, these pathways are dysregulated, promoting tumor vascularization, metastasis, and excessive collagen deposition (PubMed: 25162882). Multi-kinase inhibitors (MKIs) like nintedanib and lenvatinib are designed to simultaneously inhibit these receptors to provide a more comprehensive blockade of redundant signaling pathways. While effective, this broad-spectrum inhibition is associated with a specific toxicity profile, including cardiovascular and dermatological adverse effects (StatPearls: NBK563302). These drugs typically act by competing with ATP for the binding site within the kinase domain, thereby preventing downstream signal transduction. Clinical applications range from treating renal cell carcinoma and hepatocellular carcinoma to managing idiopathic pulmonary fibrosis.

Other names

AngiokinasesSplit-kinase domain receptorsClass III, IV, and V receptor tyrosine kinasesMulti-kinase targets

ATP-competitive inhibition of the intracellular tyrosine kinase domains of VEGFR, PDGFR, and FGFR, preventing autophosphorylation and downstream signaling cascades (e.g., MAPK/ERK, PI3K/AKT pathways).