product name SSR128129E
Description: SSR128129E (also known as SSR) is a potent, orally bioavailable and allosteric FGFR1 inhibitor with IC50 of 1.9 μM, while it does not affect other related RTKs. SSR128129E exhibits allosteric properties, including probe dependence, signaling bias, and ceiling effects. Inhibition by SSR128129E is highly conserved throughout the animal kingdom.
References: Cancer Cell. 2013 Apr 15;23(4):477-88; PLoS One. 2013 Nov 4;8(11):e80027.
346.31
Formula
C18H15N2O4.Na
CAS No.
848318-25-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 69 mg/mL (199.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
SSR
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420696
| In Vitro |
In vitro activity: SSR128129E exhibits more effective activity in cell assay due to its allosteric mechanism. SSR128129E dose-dependently inhibits FGF2-induced EC proliferation and migration with IC50 of 31 nM and 15.2 nM, respectively. As a multi-FGFR inhibitor, SSR128129E inhibits responses mediated by FGFR1-4 and thus results in the blockage of proliferation and/or migration in various cell lines including mPanc02, HEK-hFGFR2WT, PAE-hFGFR1, hB9-myeloma and HUVEC. Kinase Assay: 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-1IIIcß – 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-1IIIcß – Fc chimera soluble receptor (5 ng/assay), FGF-2 (20 ng/assay) is used for non-specific binding determinations. Cell Assay: Cell proliferation of porcine aortic endothelial (PAE) and tumor cell lines (Endothelial cells) and Panc02 tumor cells) 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. |
|---|---|
| In Vivo | In Arthritis mice, SSR128129E (30 mg/kg, p.o.) inhibits angiogenesis, inflammation, and bone resorption, and reduces the severity of clinical symptoms. In mice bearing various tumor models, SSR128129E (30 mg/kg, p.o.) inhibits both the growth of primary tumors and metastasis. In addition, SSR128129E inhibits growth of anti-VEGFR2-refractory and -sensitive tumor models, and enhances the antitumor activity of anti-VEGFR2. SSR128129E also inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice. |
| Animal model | Mouse model of Arthritic and mouse tumor model bearing pancreatic tumor cell line Panc02, murine mammary carcinoma cell line 4T1, murine colon cancer cell line CT26, or human breast MCF7/ADR cell line |
| Formulation & Dosage | Formulated in 0.6 % methylcellulose; 30 mg/kg; oral gavage |
| References | Cancer Cell. 2013 Apr 15;23(4):477-88; PLoS One. 2013 Nov 4;8(11):e80027. |
