SSR128129E

Catalog No.S7167 Batch:S716701

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Technical Data

Formula

C18H15N2O4.Na
Molecular Weight 346.31 CAS No. 848318-25-2
Solubility (25°C)* In vitro DMSO 69 mg/mL (199.24 mM)
Water 1 mg/mL (2.88 mM)
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description SSR128129E is an orally-active and allosteric FGFR1 inhibitor with IC50 of 1.9 μM, while not affecting other related RTKs.
Targets
FGFR1 [1]
1.9 μM
In vitro 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. [1]
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. [1] SSR128129E also inhibits arteriosclerosis in a mouse vein graft model and atherosclerosis in apolipoprotein E-deficient mice. [2]

Protocol (from reference)

Kinase Assay:

[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-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:

[1]
  • Cell lines

    Endothelial cells (ECs) and Panc02 tumor cells

  • Concentrations

    ~100 nM

  • Incubation Time

    72 hours

  • Method

    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.
Animal Study:

[1]
  • Animal Models

    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.

  • Dosages

    ~30 mg/kg

  • Administration

    Oral administration

Customer Product Validation

Data from [Data independently produced by , , Exp Mol Med, 2017, 49(9):e374]

Data from [Data independently produced by , , Oncogenesis, 2017, 6(1):e285]

Selleck's SSR128129E has been cited by 9 publications

FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells [ BMC Biol, 2021, 19(1):173] PubMed: 34433435
MEKK1 Regulates Chemokine Expression in Mammary Fibroblasts: Implications for the Breast Tumor Microenvironment [ Front Oncol, 2021, 11:609918] PubMed: 33868996
Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells [ Sci Rep, 2021, 11(1):6104] PubMed: 33731767
Cisplatin Resistance in Osteosarcoma: In vitro Validation of Candidate DNA Repair-Related Therapeutic Targets and Drugs for Tailored Treatments. [ Front Oncol, 2020, 10;10:331] PubMed: 32211337
VEGF pathway-targeting drugs induce evasive adaptation by activation of neuropilin-1/cMet in colon cancer cells. [ Int J Oncol, 2018, 52(4):1350-1362] PubMed: 29532881
API5 induces cisplatin resistance through FGFR signaling in human cancer cells. [Jang HS, et al. Exp Mol Med, 2017, 49(9):e374] PubMed: 28883546
API5 confers cancer stem cell-like properties through the FGF2-NANOG axis. [Song KH, et al. Oncogenesis, 2017, 6(1):e285] PubMed: 28092370
Ferulic Acid Exerts Anti-Angiogenic and Anti-Tumor Activity by Targeting Fibroblast Growth Factor Receptor 1-Mediated Angiogenesis. [ Int J Mol Sci, 2015, 16(10):24011-31] PubMed: 26473837
Integration of signals along orthogonal axes of the vertebrate neural tube controls progenitor competence and increases cell diversity [ PLoS Biol, 2014, 12(7):e1001907] PubMed: 25026549

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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