Fibroblast growth factors (FGF) are a family of cell-signaling proteins, which are involved in many processes, especially as the key factor of normal development. In addition, the FGFR family consists of a group of four homologous receptor tyrosine kinases. Besides, FGF1 was a member of a family of FGF proteins. Moreover, protein phosphorylation is a common mechanism for signaling nucleation and regulating many cellular processes. Furthermore, the inhibition of protein tyrosine kinases (PTKs) has attracted a lot of attention over the past few years as a strategy for impeding cellular proliferation. Meanwhile, c-src has been reputed to participate in PDGFR, FGFR, and EGFR mediated signal transduction pathways, and like RTKs, the abnormal regulation of c-src is relevant to neoplastic growth. PD-161570 is a potent inhibitor of FGF-1R, PDGFR, EGFR, and c-Src tyrosine kinases.
PD-161570 is a potent inhibitor of FGF-1R, PDGFR, EGFR, and c-Src tyrosine kinases.
How does PD-161570 work? Let’s study it together. In the beginning, PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM. Specifically, PD-161570 also inhibits the PDGFR, EGFR, and c-Src tyrosine kinases with IC50 values of 310 nM, 240 nM, and 44 nM, respectively. Nonetheless, PD-161570 inhibits PDGF-stimulated autophosphorylation and FGF-1 receptor phosphorylation with IC50s of 450 nM and 622 nM, respectively. Additionally, PD-161570 is also a bone morphogenetic proteins (BMPs) and TGF-β signaling inhibitor.
In addition, PD-161570 treatment inhibits PDGF-stimulated vascular smooth muscle cell proliferation in a dose-dependent fashion with an IC50 of 0.3 µM on day 8. Interestingly, PD-161570 suppresses constitutive phosphorylation of the FGF-1 receptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth of A121(p) cells in culture. Importantly, PD-161570 can potent inhibit basic fibroblast growth factor (bFGF)-mediated angiogenesis.
All in all, PD-161570 is a potent inhibitor of FGF-1R, PDGFR, EGFR, and c-Src tyrosine kinases.
References:
Hamby JM, et al.J Med Chem. 1997 Jul 18;40(15):2296-303.