SSR128129E 是一种变构和口服活性 FGFR1 抑制剂 (IC50:1.9 μM)，但不影响其他相关的 RTK。

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

在各种小鼠肿瘤模型中,SSR128129E（30 mg/kg,p.o.）可同时抑制原发性肿瘤的增殖和转移.在患有关节炎的小鼠中,SSR128129E（30 mg/kg,p.o.）抑制了炎症、血管生成和骨吸收,并缓解了临床症状.此外,SSR128129E对抗血管内皮细胞生长因子受体2顽固型肿瘤模型和敏感株的增殖有抑制作用,并增加抗血管内皮细胞生长因子受体2的抗肿瘤活性.

由于变构机制,SSR128129E在细胞实验中具有更强的活性。SSR128129剂量依赖性抑制FGF2-诱导的EC增殖和迁移（IC50：31/15.2 nM）。作为多靶点成纤维细胞生长因子受体抑制剂,SSR128129E抑制了FGFR1-4介导的反应,从而使多种细胞系的增殖和/或迁移被阻断,比如mPanc02,HEK-hFGFR2WT,PAE-hFGFR1,hB9-myeloma和人脐静脉内皮细胞株。

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)

848318-25-2

C18H15N2O4·Na

346.31

SSR

Ethanol:<1 mgml
H2O:1 mg/mL (2.88 mM)
DMSO:64 mg/mL (184.8 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years