Description
SU-5402 (215543-92-3) inhibits FGFR phosphorylation in vitro, in cell culture1, and in mouse tumor cell models2. SU-5402 can suppress ECP induced cardiomyocyte differentiation of P19CL6 embryonic carcinoma cells via an FGFR3 dependent pathway.3
Chemical Properties
Yellow-Green Solid
Uses
A specific FGFR (fibroblast growth factor receptor
er.
Definition
ChEBI: An oxindole that is 3-methyleneoxindole in which one of the hydrogens of the methylene group is substituted by a 3-(2-carboxyethyl)-4-methyl-1H-pyrrol-2-yl group. It is an ATP-competitive inhibitor of the tyrosine kinase activity of fibr
blast growth factor receptor 1.
Biological Activity
Potent and selective vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) inhibitor (IC 50 values are 0.02, 0.03, 0.51 and > 100 μ M at VEGFR2, FGFR1, PDGFR β and EGFR respectively). Inhibits embryonic left-right determination and exhibits potent anticancer activity in vitro and in vivo .
Biochem/physiol Actions
SU-5402 has inhibitory effect on the action of tyrosine kinases. It competitively binds to the ATP-binding site on the fibroblast growth factor receptor (FGFR).
in vitro
su5402 could inhibit fgfr3 phosphorylation in vitro. b cells dependent on fgfr3 for survival were sensitive to su5402 specifically. a panel of 11 human myeloma cell lines was studied, among which five beared t(4;14) translocation. the kms11 human myeloma cell line expressesing constitutively active mutant fgfr3, displayed a 95% increase in g0/g1 cells as well as 45-fold increase in apoptotic cells after su5402 treatment. in addition, the activated signal-regulated kinases 1 and 2 and signal activator of transcription 3 were down-regulated after su5402 treatment rapidly. in human myeloma cell lines with wild-type fgfr3, the stimulating effect of afgf ligand was abrogated by su5402 [1].
in vivo
balb/c mice were inoculated with syngeneic pre-b-td cells and these established tumours were treated with 300 ng/kg su5402 or carrier alone administered by either direct subcutaneous or intraperitoneal injection. tumours were collected 24 h later and western blot analyses indicated a treatment-related decrease in the levels of activated erk1/2 in the harvested tumors [1].
IC 50
0.02, 0.03, 0.51 and > 100 μm for vegfr2, fgfr1, pdgfrβ and egfr, respectively
References
1) Lee et al. (2013), Interleukin-1β enhances cell migration through AP-κ1 and NF-B pathway dependent FGF2 expression in human corneal endothelial cells; Biol. Cell, 105 175
2) Paterson et al. (2004), Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma; Br. J. Haematol., 124 595
3) Jin et al. (2012), Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway; Growth Factors, 30 344
