Platelet-derived growth factor receptor alpha, Platelet-derived growth factor receptor beta, and Fms-like tyrosine kinase 3 (PDGFRα, PDGFRβ, and FLT3)

Platelet-derived growth factor receptor alpha and beta (PDGFRα and PDGFRβ) and Fms-like tyrosine kinase 3 (FLT3) are single-pass transmembrane proteins functioning as receptor tyrosine kinases. They share a similar structure: extracellular ligand-binding domains, a transmembrane region, and a split intracellular tyrosine kinase domain. Ligand binding (e.g., PDGFs for PDGFRs, FLT3 ligand for FLT3) triggers dimerization and kinase activation, leading to cellular responses such as proliferation, survival, angiogenesis, and migration. These receptors are critically involved in development and normal tissue maintenance but are frequently mutated, rearranged, or overexpressed in cancers, making them prime targets for tyrosine kinase inhibitors. Many FDA-approved drugs and investigational compounds target these receptors in the context of leukemia, gastrointestinal stromal tumors, and other malignancies.

Other names

PDGFR-alphaCD140aPDGFR-betaCD140bFms-related tyrosine kinase 3STK-1CD135

Kinase inhibition: Most drugs inhibit the intracellular tyrosine kinase domain, blocking phosphorylation and downstream signaling. Competitive antagonism with ATP in the active site. Prevent receptor dimerization or stabilize inactive forms. Some also target mutant or fusion forms (e.g., FLT3-ITD, ETV6-PDGFRB, FIP1L1-PDGFRA fusions).