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

FGFR1:1.9 μM

SSR128129E inhibited FGF2-induced EC proliferation and migration (IC50 =31 nM) and dose-dependently induced cilia formation.SSR128129E inhibited responses mediated by FGFR1-4. For example, SSR128129E blocks the migratory response of cardiomyocytes to FGF1 (ligand for FGFR1 and FGFR4) and the capillary formation response to FGF19 (ligand for FGFR4).
SSR128129E inhibited FGF7-induced proliferation and migration of the murine pancreatic Panc02 tumor cell line, suggesting that SSR128129E also inhibits FGFR isoforms in other species.[1]

Oral administration of SSR128129E 30 mg/kg/day inhibited the growth of orthotopic Panc02 tumors by 44% starting on day 3 and delayed the growth of Lewis lung cancer. Tumor size and weight were reduced by 53% and 40%, respectively, starting on day 5.[1]
SSR128129E inhibited the growth of subcutaneous CT26 colon tumors and inhibited the growth of a multidrug-resistant MCF7/ADR breast cancer xenograft model.SSR128129E reduced the invasiveness of Panc02 tumor cells and metastasis to peritoneal lymph nodes.[1]

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)