An FGFR inhibitor
SSR 128129E is a potent inhibitor of the FGF receptor (FGFR; IC50 = 1.9 nM).1 It reduces FGF2-induced endothelial cell proliferation and migration (IC50s = 31 and 15.2 nM, respectively), as well as lamellipodia formation in vitro. SSR 128129E also reduces proliferation of PAE cells expressing FGFR1, mPanc02 cells expressing FGFR2, hB9 myeloma cells expressing FGFR3, and HUVECs expressing FGFR4 when used at a concentration of 100 nM. In vivo, SSR 128129E (30 mg/kg per day) reduces limb swelling, redness, and deformity and improves performance in an exercise endurance test in a mouse model of arthritis. It reduces tumor growth and metastasis and enhances antitumor activity of the VEGF receptor (VEGFR) antibody αVEGFR2 in a Panc02 mouse orthotopic tumor model. SSR 128129E (50 mg/kg per day) reduces atherosclerotic lesion size in the aortic sinus of apoE-/- mice.2 It also reduces intimal hyperplasia following jugular vein-to-artery bypass grafting surgery in rats.3
1.Bono, F., De Smet, F., Herbert, C.A., et al.Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric propertiesCancer Cell23(4)477-488(2013) 2.Dol-Gleizes, F., Delesque-Touchard, N., Marés, A.M., et al.A new synthetic FGF receptor antagonist inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient micePLoS One8(11)e80027(2013) 3.Huang, Q.-X., Liang, L.-D., Lan, Z.-C., et al.Effects of ssr128,129e on intimal hyperplasia in autogenous vein grafts of ratsShiyong Yixue Zazhi31(2)188-190(2015)
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