SSR128129E (SSR) is an allosteric and orally-active FGFR1 inhibitor (IC50: 1.9 μM), but not affecting other related RTKs.

FGFR1:1.9 μM

In various murine tumor models, SSR128129E (30 mg/kg, p.o.) demonstrated the ability to inhibit both the proliferation and metastasis of primary tumors. Additionally, in mice with arthritis, SSR128129E (30 mg/kg, p.o.) reduced inflammation, angiogenesis, and bone resorption, thereby alleviating clinical symptoms. Furthermore, SSR128129E also inhibited the proliferation of both resistant and sensitive strains in models of tumors with anti-vascular endothelial growth factor receptor 2 activity, enhancing the anti-tumor activity against the vascular endothelial growth factor receptor 2.

Due to its allosteric mechanism, SSR128129E exhibits enhanced activity in cell assays. It inhibits FGF2-induced proliferation and migration of endothelial cells in a dose-dependent manner, with an IC50 of 31/15.2 nM. As a multitarget fibroblast growth factor receptor (FGFR) inhibitor, SSR128129E blocks responses mediated by FGFR1-4, thus inhibiting proliferation and/or migration across various cell lines, including mPanc02, HEK-hFGFR2WT, PAE-hFGFR1, hB9-myeloma, and human umbilical vein endothelial cell lines.

Scintillation Proximity Assay, 125I-FGF-2 Binding: SPA protein A beads are supplied as a suspension in PBS at 20 mg/mL, then diluted with binding buffer (KCl, 400 mg/L; MgSO4 200 mg/L; NaCl 6.4 g/L; NaHCO3 3.7 g/L; NaH2PO4 0.141 mg/mL; bis Tris Propane 11.292 g/L; Glucose 4.5 g/L; Gelatin 0.1 %; pH 7.0) at 10 mg/mL. 125I-FGF-2 radioligand and FGFR-1IIIc? - Fc Chimera are diluted into binding buffer. Binding was performed on 96-well plates coated with 0.1 % gelatin. Total assay volume is 0.1 mL. Binding of 125I-FGF-2 is determined by incubation of SPA beads coated with protein A (0.5 mg/assay) with FGFR-1IIIc? - Fc chimera soluble receptor (5 ng/assay), FGF-2 (20 ng/assay) is used for non-specific binding determinations.

Cell proliferation of porcine aortic endothelial (PAE) and tumor cell lines is analyzed on exponentially growing cells that are starved for 16 hours in 0.2 % FBS containing medium and seeded at 4,000 cells/well in 96-well microplates. After exposure to mitogens and/or SSR for 72 hours, cell proliferation is assessed with the use of the CellTiter 96 AQueous One Solution Cell Proliferation Assay according to manufacturer’s instructions. 10 % FBS containing medium is used a positive control. (Only for Reference)