Platelet-derived growth factor receptor (PDGFR), Colony-stimulating factor 1 receptor (CSF1R), and Ephrin type-A receptor 2 (EPHA2) (PDGFR/CSF1R/EPHA2)

The target profile comprising Platelet-Derived Growth Factor Receptor (PDGFR), Colony-Stimulating Factor 1 Receptor (CSF1R/c-FMS), and Ephrin type-A receptor 2 (EPHA2) represents a cluster of receptor tyrosine kinases (RTKs) central to oncogenesis and the tumor microenvironment (UniProt P09619, P07333, P29317). PDGFR isoforms are critical for mesenchymal cell proliferation and are frequently implicated in the growth of gliomas and sarcomas (PubMed PMID: 24513176). CSF1R, also known as c-FMS, regulates the survival and differentiation of macrophages, facilitating the recruitment of tumor-associated macrophages (TAMs) that promote immunosuppression and metastasis (NIH/NCI). EPHA2 is involved in cell-cell adhesion and migration, often overexpressed in aggressive epithelial tumors where it contributes to vasculogenic mimicry and drug resistance (PubMed PMID: 25639196). Drugs targeting this multi-kinase group, such as Dasatinib or Sunitinib, function by binding to the ATP-binding pocket of the kinase domain, thereby inhibiting downstream signaling pathways like PI3K/AKT and Ras/MAPK (PubChem CID 10635). These inhibitors are used to treat various malignancies, including chronic myeloid leukemia and gastrointestinal stromal tumors, though they are associated with safety concerns like myelosuppression and fluid retention (StatPearls).

Other names

PDGFRc-FMSCSF1REPHA2Tyrosine-protein kinase FmsEphrin type-A receptor 2Platelet-derived growth factor receptorSecondary tyrosine kinases

Small molecule inhibition of the intracellular kinase domain through ATP-competitive binding, preventing autophosphorylation and subsequent activation of downstream signaling pathways like PI3K/AKT and MAPK/ERK.