Vascular endothelial growth factor receptor 1-3 (VEGFR1-3), fibroblast growth factor receptor 1-4 (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), and proto-oncogene c-Kit (KIT) (VEGFR1-3/FGFR1-4/PDGFRα/KIT)

This target profile comprises a group of receptor tyrosine kinases (RTKs) that are essential for mediating cellular responses to growth factors involved in angiogenesis, lymphangiogenesis, and tissue remodeling. The Vascular Endothelial Growth Factor Receptors (VEGFR1-3) are the primary drivers of blood vessel formation and permeability, which are often hijacked by tumors to support growth (Source: UniProt). Fibroblast Growth Factor Receptors (FGFR1-4) and Platelet-Derived Growth Factor Receptor alpha (PDGFRα) contribute to cell proliferation, survival, and the activation of fibroblasts, making them key players in both malignancy and fibrotic diseases like idiopathic pulmonary fibrosis (Source: PubMed, PMID: 25162880). The proto-oncogene c-Kit (KIT) is a cytokine receptor vital for the maintenance of hematopoietic stem cells and mast cell signaling (Source: StatPearls). Dysregulation or over-expression of these receptors is frequently observed in various cancers, including renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. Drugs targeting this specific multi-kinase profile, such as lenvatinib, act by binding to the intracellular ATP-binding pocket of these receptors, thereby blocking downstream signaling pathways like MAPK and PI3K/AKT (Source: PubChem). This simultaneous inhibition helps to overcome redundant signaling pathways that tumors use to escape single-target therapies.

Other names

Multi-kinase targetAngiokinase receptorsRTK profileTriple angiokinase inhibitor profile

Competitive inhibition of the intracellular tyrosine kinase domains by competing with ATP for binding, thereby preventing autophosphorylation and downstream signaling cascades (Source: PubMed).