Vascular endothelial growth factor receptor 1-3, Platelet-derived growth factor receptor, Fibroblast growth factor receptor, RAF kinase, and Proto-oncogene c-Kit (VEGFR/PDGFR/FGFR/RAF/KIT)

The target profile comprising Vascular Endothelial Growth Factor Receptors (VEGFR1-3), Platelet-Derived Growth Factor Receptors (PDGFR), Fibroblast Growth Factor Receptors (FGFR), RAF kinases, and the Proto-oncogene c-Kit (KIT) represents a comprehensive set of signaling molecules involved in tumor progression. VEGFR and FGFR are primary drivers of angiogenesis and lymphangiogenesis, facilitating the development of the vascular network necessary for tumor growth and metastasis (UniProt, 2024). PDGFR and KIT contribute to the recruitment of stromal cells and the maintenance of the tumor microenvironment, while RAF kinases (specifically BRAF and CRAF) are essential mediators of the MAPK/ERK pathway, which regulates cell proliferation and survival (PubMed, 2023). Drugs targeting this broad array of kinases, known as multi-kinase inhibitors (MKIs), are designed to simultaneously inhibit multiple pathways to prevent tumor escape and overcome signaling redundancy. These agents, such as sorafenib and regorafenib, are clinically utilized to treat various solid tumors, including renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumors (NIH, 2024). Despite their efficacy, the broad-spectrum inhibition of these kinases often leads to characteristic systemic toxicities, including hypertension and hand-foot skin reactions, which require careful clinical management (StatPearls, 2024).

Other names

Multi-kinase inhibitor target profileVEGFR-PDGFR-FGFR-RAF-KIT axisAngiogenesis and proliferation kinase cluster

ATP-competitive inhibition of the intracellular catalytic kinase domains of multiple receptor tyrosine kinases and serine/threonine kinases, effectively blocking downstream signaling through the MAPK/ERK and PI3K/AKT pathways (PubChem, 2024).