219580-11-7

PD173074 (219580-11-7) is an inhibitor of FGFR tyrosine kinase, and to a lesser extent VEGFR1?(IC50?values are 5 nM, 22.5 nM and 100 nM for FGFR1, FGFR3 and VEGFR respectively). Inhibition of FGFR by PD173074 promotes stem cell self renewal.2,3

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A cell-permeable compound that acts as a potent, ATP-competitive, and reversible inhibitor of FGF and VEGF receptors. PD 173074 inhibits PDGFR and c-Src only at much higher concentration. Shown to inhibit the autophosphorylation of endogenous FGFR1 and overexpressed VEGFR2.

A selective FGFR1 and

PD 173074 ar signal-related kinase phosphorylation.

PD173074 is a potent FGFR1 inhibitor with IC50 of ~25 nM and also inhibits VEGFR2 with IC50 of 100-200 nM.

ChEBI: A member of the class of ureas that is 1-tert-butylurea in which one of the hydrogens attached to N3 is substituted by a pyrido[2,3-d]pyrimidin-7-yl group, which is itself substituted at pos tions 2 and 6 by a 4-(diethylamino)butyl]amino group and a 3,5-dimethoxyphenyl group, respectively. It is a FGF/VEGF receptor tyrosine kinase inhibitor.

Selective FGFR1 and FGFR3 inhibitor (IC 50 values are 5, 21.5, ~100, 17600 and 19800 nM for FGFR3, FGFR1, VEGFR2, PDGFR and c-Src respectively, and > 50000 nM for EGFR, InsR, MEK and PKC). Inhibits VEGF- and FGF-induced angiogenesis in the mouse cornea model of angiogenesis. Inhibits proliferation and differentiation of oligodendrocyte progenitors.

PD 173074 is a fibroblast growth factor receptor 3 (FGFR3) inhibitor: IC50 = 5 nM inhibition of FGFR3 autophosphorylation. PD 173074 arrests the G0/G1 phase of FGFR3-expressing cells. It is 100-fold more selective for FGFR3 than for VEGF receptors, IGF-1 receptors, and MAPKs.

pd173074 was found to block h-510 and h-69 sclc proliferation and clonogenic growth in a dose-dependent fashion and prevent fgf-2-induced chemoresistance as well. these effects correlate with the inhibition of both fgfr1 and fgfr2 transphosphorylation. in addition, pd173074 showed a high degree of selectivity for fgfr tyrosine kinase [2].

This pyrido[2,3-d]pyrimidine (FWfree-base = 523.68 g/mol; CAS 219580-11- 7; Solubility: 100 mM in DMSO, 100 mM in ethanol), also known as N-[2- [[4- (diethylamino) butyl]amino]-6- (3,5-dimethoxyphenyl) pyrido[2,3- d]pyrimidin-7-yl]-N'- (1,1-dimethylethyl) urea, inhibits the fibroblast growth factor receptor protein-tyrosine kinase and vascular endothelial growth factor receptor protein-tyrosine kinase. PD173074 inhibits FGF-2- mediated effects on proliferation, differentiation, as well as MAPK activation in oligodendrocyte-lineage cells. It likewise inhibits fibroblast growth factor receptor-3, inducing differentiation and apoptosis in t (4;14) myeloma. PD173074 also selectively inhibits fibroblast growth factor receptor-3 (FGFR3) tyrosine kinase. It inhibits proliferation of bladder cancer cell carrying the FGFR3 gene mutation along with up- regulation of p27/Kip1 and G1/G0 arrest. PD173074 blocks small cell lung cancer growth in vitro and in vivo.

in the h-510 xenograft mouse model, tumor growth was significanlty improved similar to that seen with single-agent cisplatin administration. accordingly, pd173074 treatment resulted in significanlty prolonged median survival when compared with that of control sham-treated animals. more dramatically, pd173074 also induced complete responses lasting >6 months in 50% of in mice h-69 xenografts [2].

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1 Bansal?et al. (2003),?Specific inhibitor of FGF receptor signaling: FGF-2 mediated effects on proliferation, differentiation and MAPK activation are inhibited by PD173074 in oligodendrocyte-lineage cells; J. Neurosci. Res.,?74?486 2) Kim?et al. (2012),?Regulation of autocrine fibroblast growth factor-2 signaling by perfusion flow in 3D human mesenchymal stem cell constructs; Biotechnol. Prog.,?28?1384 3) Zaragosi?et al. (2006),?Autocrine fibroblast growth factor 2 signaling is critical for self renewal of human multipotent adipose-derived stem cells; Stem Cells,?24?2412