SSR128129E

For research use only.

Catalog No.S7167 Synonyms: SSR

5 publications

Molecular Weight(MW): 346.31

SSR128129E is an orally-active and allosteric FGFR1 inhibitor with IC50 of 1.9 μM, while not affecting other related RTKs.

Selleck's SSR128129E has been cited by 5 publications

Front Oncol, 2020, 10;10:331

PubMed: 32211337 ( click the link to review the publication )

Int J Oncol, 2018, 52(4):1350-1362

PubMed: 29532881 ( click the link to review the publication )

Exp Mol Med, 2017, 49(9):e374

PubMed: 28883546 ( click the link to review the publication )

Oncogenesis, 2017, 6(1):e285

PubMed: 28092370 ( click the link to review the publication )

Int J Mol Sci, 2015, 16(10):24011-31

PubMed: 26473837 ( click the link to review the publication )

2 Customer Reviews

Western blot analysis of the expression and activation status (a) of pFGFR, pERK and Bim after treatment of API5-overexpressing cells (a) with either DMSO or SSR128129E.

Exp Mol Med, 2017, 49(9):e374. SSR128129E purchased from Selleck.

(a, d) Cells were treated with indicated concentrations of SSR128129E for 48 h. Cell viability was measured by an MTT assay, and then the concentrations resulting in 50% inhibition of cell viability (IC50 values) were determined. (b, e) Cells were treated with 10 μM of SSR128129E for 12 h. Expression levels of NANOG, pFGFR, FGFR, pERK and ERK in these cells were analyzed by western blot analysis. Numbers below blots indicate the expression as measured by fold change. (c, f) Cells were treated with 10 μM of SSR128129E for 12 h. Flow cytometry analysis of CD44 in these cells. Error bars represent mean±s.d. Data presented are representative of three independent experiments

Oncogenesis, 2017, 6(1):e285. SSR128129E purchased from Selleck.

Purity & Quality Control

Choose Selective FGFR Inhibitors

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]

Assay

Methods	Test Index	PMID
Western blot	pFGFR1 / FGFR1 / pERK / ERK / NANOG ; PubMed: 28092370 Oncogenesis (b, e) Cells were treated with 10 um of SSR128129E for 12 h. Expression levels of NANOG, pFGFR, FGFR, pERK and ERK in these cells were analyzed by western blot analysis. Numbers below blots indicate the expression as measured by fold change.	28092370
Growth inhibition assay	Cell viability; PubMed: 28092370 Oncogenesis (a, d) Cells were treated with indicated concentrations of SSR128129E for 48 h. Cell viability was measured by an MTT assay, and then the concentrations resulting in 50% inhibition of cell viability (IC50 values) were determined.	28092370

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

Kinase Assay: ^[1]	- Collapse 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 Research: ^[1]	- Collapse 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. (Only for Reference)
Animal Research: ^[1]	- Collapse 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 (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	69 mg/mL (199.24 mM)
	Water	1 mg/mL (2.88 mM)
	Ethanol	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.

Chemical Information Download SSR128129E SDF

Molecular Weight	346.31
Formula	C₁₈H₁₅N₂O₄.Na
CAS No.	848318-25-2
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	SSR
Smiles	COC1=C2C=CC=C[N]2C(=C1C)C(=O)C3=CC=C(N)C(=C3)C(=O)O[Na]

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-05-15)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04307394	Not yet recruiting	Behavioral: LifePlans	Suicide\|Psychiatric Hospitalization	Butler Hospital\|National Institute of Mental Health (NIMH)	November 1 2020	Not Applicable
NCT04308304	Not yet recruiting	Drug: MK-1942\|Drug: Donepezil\|Drug: Placebo	Alzheimer''s Disease	Merck Sharp & Dohme Corp.	October 13 2020	Phase 1
NCT04373616	Not yet recruiting	Biological: ACI-24\|Biological: Placebo	Down Syndrome	AC Immune SA	October 2020	Phase 2
NCT04118088	Not yet recruiting	Biological: Darvadstrocel	Crohn''s Disease\|Complex Perianal Fistula	Millennium Pharmaceuticals Inc.\|Takeda	August 14 2020	Phase 4
NCT04374253	Not yet recruiting	Drug: Gantenerumab	Alzheimer Disease	Hoffmann-La Roche	August 3 2020	Phase 3

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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FGFR Signaling Pathway Map

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SSR128129E