SSR128129E
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MedKoo CAT#: 406387

CAS#: 848318-25-2 (sodium)

Description: SSR128129E (SSR) is an potent FGFR inhibitor, which inhibits fibroblast growth factor receptor (FGFR) signaling by binding to the extracellular FGFR domain without affecting orthosteric FGF binding. SSR128129E exhibits allosteric properties, including probe dependence, signaling bias, and ceiling effects. Inhibition by SSR128129E is highly conserved throughout the animal kingdom. Oral delivery of SSR128129E inhibits arthritis and tumors that are relatively refractory to anti-vascular endothelial growth factor receptor-2 antibodies. Thus, orally-active extracellularly acting small-molecule modulators of RTKs with allosteric properties can be developed and may offer opportunities to improve anticancer treatment.


Chemical Structure

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SSR128129E
CAS# 848318-25-2 (sodium)

Theoretical Analysis

MedKoo Cat#: 406387
Name: SSR128129E
CAS#: 848318-25-2 (sodium)
Chemical Formula: C18H16N2O4
Exact Mass: 324.11101
Molecular Weight: 324.33
Elemental Analysis: C, 66.66; H, 4.97; N, 8.64; O, 19.73

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1250.0 Ready to ship
500.0mg USD 2650.0 Ready to ship
1.0g USD 3750.0 Ready to ship
2.0g USD 6250.0 2 Weeks
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Related CAS #: 848463-13-8 (free)   848318-25-2 (sodium)    

Synonym: SSR128129E; SSR 128129E; SSR-128129E.

IUPAC/Chemical Name: sodium 2-amino-5-(1-methoxy-2-methylindolizine-3-carbonyl)benzoate

InChi Key: JFBMSTWZURKQOC-UHFFFAOYSA-M

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

SMILES Code: O=C([O-])C1=CC(C(C2=C(C)C(OC)=C3C=CC=CN23)=O)=CC=C1N.[Na+]

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in water

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: SSR128129E is a FGFR inhibitor with an IC50 of 1.9 μM for FGFR1.
In vitro activity: Treating radioresistant U87 and SF763 glioblastoma cells with the FGFR inhibitor, SSR12819E, radiosensitised these cells while the survival after irradiation of the more radiosensitive U251 and SF767 cells was not affected. SSR128129E administration to U87 cells increased the radiation-induced mitotic cell death. It also decreased cell membrane availability of the FGFR-1 mainly expressed in these cells, increased this receptor's ubiquitylation, inhibited radiation-induced RhoB activation and modulated the level of hypoxia inducible factor, HIF-1α, a master regulator of hypoxia, thus suggesting a role of FGFR in the regulation of hypoxia pathways. Reference: Eur J Cancer. 2014 Sep;50(13):2351-9. https://www.ejcancer.com/article/S0959-8049(14)00662-5/fulltext
In vivo activity: Treating orthotopically U87 xenografted mice with SSR128129E before two subsequent local 2.5Gy irradiations significantly increased the animals neurological sign free survival (NSFS) compared to the other groups of treatment. These results strongly suggest that targeting FGFR with the FGFR blocker SSR128129E might represent an interesting strategy to improve the efficiency of radiotherapy in glioblastoma. Reference: Eur J Cancer. 2014 Sep;50(13):2351-9. https://www.ejcancer.com/article/S0959-8049(14)00662-5/fulltext

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 51.0 157.25
DMF 30.0 92.5
Ethanol 1.0 3.08
Water 1.0 3.08
PBS (pH 7.2) 1.0 3.08

Preparing Stock Solutions

The following data is based on the product molecular weight 324.33 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C. Preclinical evidence that SSR128129E--a novel small-molecule multi-fibroblast growth factor receptor blocker--radiosensitises human glioblastoma. Eur J Cancer. 2014 Sep;50(13):2351-9. doi: 10.1016/j.ejca.2014.05.012. Epub 2014 Jun 18. PMID: 24953334.
In vitro protocol: 1. Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C. Preclinical evidence that SSR128129E--a novel small-molecule multi-fibroblast growth factor receptor blocker--radiosensitises human glioblastoma. Eur J Cancer. 2014 Sep;50(13):2351-9. doi: 10.1016/j.ejca.2014.05.012. Epub 2014 Jun 18. PMID: 24953334.
In vivo protocol: 1. Ader I, Delmas C, Skuli N, Bonnet J, Schaeffer P, Bono F, Cohen-Jonathan-Moyal E, Toulas C. Preclinical evidence that SSR128129E--a novel small-molecule multi-fibroblast growth factor receptor blocker--radiosensitises human glioblastoma. Eur J Cancer. 2014 Sep;50(13):2351-9. doi: 10.1016/j.ejca.2014.05.012. Epub 2014 Jun 18. PMID: 24953334.

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1: Dol-Gleizes F, Delesque-Touchard N, Marès AM, Nestor AL, Schaeffer P, Bono F. A New Synthetic FGF Receptor Antagonist Inhibits Arteriosclerosis in a Mouse Vein Graft Model and Atherosclerosis in Apolipoprotein E-Deficient Mice. PLoS One. 2013 Nov 4;8(11):e80027. doi: 10.1371/journal.pone.0080027. PubMed PMID: 24224032; PubMed Central PMCID: PMC3817113.

2: Herbert C, Alcouffe C, Bono F. [SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling]. Med Sci (Paris). 2013 Oct;29(10):834-6. doi: 10.1051/medsci/20132910007. Epub 2013 Oct 18. French. PubMed PMID: 24148118.

3: Herbert C, Schieborr U, Saxena K, Juraszek J, De Smet F, Alcouffe C, Bianciotto M, Saladino G, Sibrac D, Kudlinzki D, Sreeramulu S, Brown A, Rigon P, Herault JP, Lassalle G, Blundell TL, Rousseau F, Gils A, Schymkowitz J, Tompa P, Herbert JM, Carmeliet P, Gervasio FL, Schwalbe H, Bono F. Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling. Cancer Cell. 2013 Apr 15;23(4):489-501. doi: 10.1016/j.ccr.2013.02.018. PubMed PMID: 23597563.

4: Bono F, De Smet F, Herbert C, De Bock K, Georgiadou M, Fons P, Tjwa M, Alcouffe C, Ny A, Bianciotto M, Jonckx B, Murakami M, Lanahan AA, Michielsen C, Sibrac D, Dol-Gleizes F, Mazzone M, Zacchigna S, Herault JP, Fischer C, Rigon P, Ruiz de Almodovar C, Claes F, Blanc I, Poesen K, Zhang J, Segura I, Gueguen G, Bordes MF, Lambrechts D, Broussy R, van de Wouwer M, Michaux C, Shimada T, Jean I, Blacher S, Noel A, Motte P, Rom E, Rakic JM, Katsuma S, Schaeffer P, Yayon A, Van Schepdael A, Schwalbe H, Gervasio FL, Carmeliet G, Rozensky J, Dewerchin M, Simons M, Christopoulos A, Herbert JM, Carmeliet P. Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties. Cancer Cell. 2013 Apr 15;23(4):477-88. doi: 10.1016/j.ccr.2013.02.019. PubMed PMID: 23597562.

5: Mohan SK, Rani SG, Chiu IM, Yu C. WITHDRAWN: Interaction of FGF1 with a novel anti-angiogenic drug SSR128129E. Arch Biochem Biophys. 2012 Jun 5. [Epub ahead of print] PubMed PMID: 22683470.



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