PD-089828

PD-089828 is an ATP competitive inhibitor of FGFR-1, PDGFR-β and EGFR (IC50s=0.15, 1.76, and 5.47 µM, respectively) and a noncompetitive inhibitor of c-Src tyrosine kinase (IC50=0.18 µM). PD 089828 also inhibits MAPK with an IC50 of 7.1 µM. PD-089828 inhibits PDGF-, EGF- and bFGF-mediated tyrosine kinase receptor autophosphorylation in vitro[1].

Research Areas >> Cancer

Signaling Pathways >> JAK/STAT Signaling >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> EGFR

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> Src

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR

FGFR1:0.15 μM (IC50)

PDGFR-β:1.76 μM (IC50)

EGFR:5.47 μM (IC50)

c-Src:0.18 μM (IC50)

PD-089828 (0.5-20 µM; 2 hours) inhibits PDGFR autophosphorylation with an IC50 of 0.82 µM[1]. PD-089828 (1-50 µM; 2 hours) inhibits EGFR autophosphorylation with an IC50 value of 10.9 µM[1]. In A121(p) cells, PD 089828 potently inhibits the phosphorylation of FGFR-1 with an IC50 value of 0.63 µM[1].PD-089828 (10 µM; 8 days) produces a concentration-related inhibition of serum-stimulated cell growth with an IC50 value of 1.8 µM[1]. PD-089828 inhibits increases in DNA synthesis stimulated by all three growth factors, with IC50 values of 0.8 for PDGF-, 1.7 for EGF- and 0.48 µM for bFGF-induced mitogenesis[1]. Cell Proliferation Assay[1] Cell Line: Vascular smooth muscle cells (serum-stimulated growth) Concentration: 10 µM Incubation Time: 8 consecutive days Result: Produced a concentration-related inhibition of serum-stimulated cell growth with an IC50 value of 1.8 µM. Western Blot Analysis[1] Cell Line: Vascular smooth muscle cells (stimulated with PDGF-BB 30 ng/ml) Concentration: 0.5-20 µM Incubation Time: 2 hours Result: Inhibited PDGFR autophosphorylation with an IC50 of 0.82 µM.

[1]. Dahring TK, et al. Inhibition of growth factor-mediated tyrosine phosphorylation in vascular smooth muscle by PD 089828, a new synthetic protein tyrosine kinase inhibitor. J Pharmacol Exp Ther. 1997 Jun;281(3):1446-56.