Inhibitor of tyrosine kinase activity of fibroblast growth factor receptors
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PD 173074

Item No. 13032

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
N-[2-[[4-(diethylamino)butyl]amino]-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl]-N'-(1,1-dimethylethyl)-urea
CAS Number
219580-11-7
Molecular Formula
C28H41N7O3
Formula Weight
523.7
Purity
≥95%
Formulation (Request formulation change)
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMSO: 1 mg/mLEthanol: 25 mg/mL
λmax
238, 284, 368 nm
SMILES
CCN(CC)CCCCNc1ncc2cc(c3cc(OC)cc(OC)c3)c(NC(=O)NC(C)(C)C)nc2n1
InChi Code
InChI=1S/C28H41N7O3/c1-8-35(9-2)13-11-10-12-29-26-30-18-20-16-23(19-14-21(37-6)17-22(15-19)38-7)25(31-24(20)32-26)33-27(36)34-28(3,4)5/h14-18H,8-13H2,1-7H3,(H3,29,30,31,32,33,34,36)
InChi Key
DXCUKNQANPLTEJ-UHFFFAOYSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    5 mg

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    Product Description

    The fibroblast growth factor receptors (FGFRs) are cell surface receptors with intrinsic tyrosine kinase activity, which is necessary for receptor activation and signal propagation. PD 173074 is a potent and selective inhibitor of FGFR tyrosine kinase activity, blocking autophosphorylation of FGFR1 with an IC50 value of 21.5 nM.1 For comparison, it weakly inhibits PDGFR and c-Src (IC50 = 17.6 and 19.8 μM, respectively) and has no effect on EGFR, InsR, MEK, or PKC.1 PD 173074 also prevents signaling, at nanomolar levels, through FGFR2-5.2,3,4,5,6 Inhibition of FGFR signaling using PD 173074, impairs angiogenesis as well as self-renewal of stem cells via ERK1/2 activation.2,5,6,7,8

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Mohammadi, M., Froum, S., Hamby, J.M., et al. Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain. EMBO J. 17(20), 5896-5904 (1998).

    2. Skaper, S.D., Kee, W.J., Facci, L., et al. The FGFR1 inhibitor PD 173074 selectively and potently antagonizes FGF-2 neurotrophic and neurotropic effects. J. Neurochem. 75, 1520-1527 (2000).

    3. Koziczak, M., Holbro, T., and Hynes, N.E. Blocking of FGFR signaling inhibits breast cancer cell proliferation through downregulation of D-type cyclins. Oncogene 23, 3501-3508 (2004).

    4. Grand, E.K., Chase, A.J., Heath, C., et al. Targeting FGFR3 in multiple myeloma: inhibition of t(4;14)-positive cells by SU5402 and PD173074. Leukemia 18, 962-966 (2004).

    5. St.Bernard, R., Zheng, L., Liu, W., et al. Fibroblast growth factor receptors as molecular targets in thyroid carcinoma. Endocrinology 146(3), 1145-1153 (2005).

    6. Stavridis, M.P., Lunn, J.S., Collins, B.J., et al. A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification. Development 134, 2889-2894 (2007).

    7. Kunath, T., Saba-El-Leil, M.K., Almousailleakh, M., et al. FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment. Development 134, 2895-2902 (2007).

    8. Zaragosi, L.E., Ailhaud, G., and Dani, C. Autocrine fibroblast growth factor 2 signaling is critical for self-renewal of human multipotent adipose-derived stem cells. Stem Cells 24, 2412-2419 (2006).