| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
SSR128129E (also known as SSR-128129E; SSR 128129 E) is a novel, potent, orally bioavailable and allosteric FGFR1 inhibitor with potential anticancer and anti-inflammatory activity. With an IC50 of 1.9 μM, it inhibits FGFR1, but has no effect on other related RTKs. The pancreatic tumor cell line Panc02, the murine mammary carcinoma cell line 4T1, the murine colon cancer cell line CT26, or the human breast MCF7/ADR cell line all demonstrate high in vivo efficacy in these models of arthritis in mice and tumors in mice.
| Targets |
FGFR1 (IC50 = 1.9 μM); FGFR2; FGFR3; FGFR4
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| ln Vitro |
SSR128129E shows greater efficacy in the cell assay because of its allosteric mechanism. With an IC50 of 15.2 nM and 31 nM, respectively, SSR128129E dose-dependently suppresses FGF2-induced EC migration and proliferation. SSR128129E is a multi-FGFR inhibitor that suppresses responses mediated by FGFR1-4. This prevents proliferation and/or migration in a number of cell lines, including mPanc02, HEK-hFGFR2WT, PAE-hFGFR1, hB9-myeloma, and HUVEC.[1]
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| ln Vivo |
SSR128129E (30 mg/kg, p.o.) decreases the severity of clinical symptoms in arthritis-affected mice by inhibiting angiogenesis, inflammation, and bone resorption. SSR128129E (30 mg/kg, p.o.) inhibits the growth of primary tumors as well as metastasis in mice with different tumor models. Furthermore, SSR128129E increases the antitumor activity of anti-VEGFR2 and suppresses the growth of anti-VEGFR2-refractory and -sensitive tumor models.[1] Additionally, SSR128129E prevents atherosclerosis in mice lacking apolipoprotein E and arteriosclerosis in a mouse vein graft model.[2]
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| Enzyme Assay |
The SPA protein A beads are supplied as a suspension in PBS at a concentration of 20 mg/mL. They are subsequently diluted at a concentration of 10 mg/mL 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). Binding buffer is used to dilute the FGFR-1IIIcß-Fc Chimera and 125I-FGF-2 radioligand. On 96-well plates coated with 0.1% gelatin, binding was done. The assay's total volume is 0.1 milliliters. The assay for determining the binding of 125I-FGF-2 involves incubating 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 utilized for non-specific binding determinations.
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| Cell Assay |
Porcine aortic endothelial (PAE) and tumor cell lines are used to analyze the proliferation of exponentially growing cells that are seeded at 4,000 cells/well in 96-well microplates and starved for 16 hours in a medium containing 0.2% FBS. The CellTiter 96 AQueous One Solution Cell Proliferation Assay is used in accordance with the manufacturer's instructions to measure cell proliferation following a 72-hour exposure to mitogens and/or SSR. A positive control is a medium containing 10% FBS.
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| Animal Protocol |
Mice: Mouldered 4T1 mammary carcinoma cells are injected into anesthetized BALB/c mice. Rationale: SSR128129E or vehicle (0.6 % methylcellulose) is given orally every day by gavage to tumor-bearing mice at a dose of 30 mg/kg until day 21, when the experiment comes to an end. The mice are randomly assigned for tumor size on day 5 after tumor cell inoculation. Tumor volume is quantified. After the experiment is over, the tumors and lungs are removed from the mice that were sacrificed with a pentobarbital injection. Examining the lungs under a dissecting microscope allows one to count any visible metastatic nodules.
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| References | |
| Additional Infomation |
Sodium 2-amino-5-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]benzoate is an organic sodium salt having 2-amino-5-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]benzoate as the counterion. It has a role as an antineoplastic agent and a fibroblast growth factor receptor antagonist. It contains a 2-amino-5-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]benzoate.
FGFR Inhibitor is any agent that inhibits the fibroblast growth factor receptor (FGFR). |
| Molecular Formula |
C18H16N2O4
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|---|---|---|
| Molecular Weight |
346.31
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| Exact Mass |
346.092
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| Elemental Analysis |
C, 66.66; H, 4.97; N, 8.64; O, 19.73
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| CAS # |
848318-25-2
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| Related CAS # |
SSR128129E free acid;848463-13-8
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| PubChem CID |
68853159
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| Appearance |
Yellow solid powder
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| LogP |
2.014
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
504
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[Na].O=C(C1C(N)=CC=C(C(C2N3C(C=CC=C3)=C(OC)C=2C)=O)C=1)O
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| InChi Key |
JFBMSTWZURKQOC-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C18H16N2O4.Na/c1-10-15(20-8-4-3-5-14(20)17(10)24-2)16(21)11-6-7-13(19)12(9-11)18(22)23;/h3-9H,19H2,1-2H3,(H,22,23);/q;+1/p-1
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| Chemical Name |
sodium;2-amino-5-(1-methoxy-2-methylindolizine-3-carbonyl)benzoate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8876 mL | 14.4379 mL | 28.8759 mL | |
| 5 mM | 0.5775 mL | 2.8876 mL | 5.7752 mL | |
| 10 mM | 0.2888 mL | 1.4438 mL | 2.8876 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Effect of SSR128129E on neointimal proliferation in the vein graft model. PLoS One. 2013; 8(11): e80027. |
Lesion morphology and size in the aortic sinus of 6 month old apoE-deficient mice. PLoS One. 2013 Nov 4;8(11):e80027. |
mRNA expression levels of FGF receptors and ligands in the aortic sinus. PLoS One. 2013 Nov 4;8(11):e80027. |
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