An Overview of PDGFR
Platelet-derived growth factor receptor (PDGFR) is a tyrosine kinase receptor with protein tyrosine kinase activity. PDGFR is composed of a domain specifically recognized by the extracellular N-terminus and PDGF, an intermediate hydrophobic domain of a single-stranded sequence transmembrane, and a peptide domain with a tyrosine protein kinase activity at the C-terminus of the cell. Platelet-derived growth factor (PDGF) belongs to the vascular endothelial growth factor family with important activity in cancer and leukemia. PDGF is one of the essential factors influencing the initial stage of atherosclerosis, and it is also the strongest mitogenic factor of hepatic stellate cells. When PDGF binds to the ligand PDGF, it activates and amplifies the signal through specific tyrosine residue dephosphorylation, promotes actin rearrangement and exerts physiological functions such as mitosis and chemotaxis.
Major types of PDGFR
PDGFR consists of two subunits, α and β. These two structurally related tyrosine kinase receptors have different binding affinities to the four single strands of PDGF. PDGFR homodimer and heterodimer manifestations include PDGFR-αα, PDGFR -ββ and PDGFR -αβ.
Inhibition of PDGFR
PDGFR inhibitors can inhibit PDGF signal transduction, down-regulate tumor growth and proliferation signals, inhibit tumor angiogenesis, and promote tumor cell apoptosis. PDGFR inhibitors have the advantages of high selectivity and low toxic side effects. PDGFR inhibitors can be divided into two categories based on their mechanism of action. One is a competitive inhibitor of ATP that targets the ATP-binding site of PDGFR kinase and blocks the phosphorylation process. The other is a PDGF antagonist, which is structurally similar to the PDGF subtype and inhibits the binding of PDGF to PDGFR. PDGFR inhibitors are mainly composed of quinoxalines, quinazolines, anthraquinones, and benzimidazoles. There are also inhibitors that mimic the structural features of the PDGF subtype.
PDGFR and diseases
Overexpression of the PDGF and PDGFR families is closely related to a range of diseases such as malignant tumors, atherosclerosis, arterial restenosis, and fibrosis. At present, PDGF signaling is mainly reduced by inhibiting PDGFR and blocking its tyrosine kinase phosphorylation and downstream signal transduction, and PDGFR has become a drug target for the treatment of tumor diseases.
Bergsten E., Uutela M., Li X., Kristian P., Arne Ö., Carl-Henrik H., Kari A., Ulf E. (2001) PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol, 3(5): 512-516.
Products for PDGFR