SSR128129E | CAS#848318-25-2 | FGFR inhibitor

MedKoo Cat#: 406387 | Name: SSR128129E

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

SSR128129E

CAS#848318-25-2 (sodium)

Theoretical Analysis

MedKoo Cat#: 406387

Name: SSR128129E

CAS#: 848318-25-2 (sodium)

Chemical Formula: C18H16N2O4

Exact Mass: 324.1110

Molecular Weight: 324.33

Elemental Analysis: C, 66.66; H, 4.97; N, 8.64; O, 19.73

Price and Availability

Size	Price	Availability
10mg	USD 110.00	Ready to ship
25mg	USD 220.00	Ready to ship
50mg	USD 385.00	Ready to ship
100mg	USD 685.00	Ready to ship
200mg	USD 1,250.00	Ready to ship

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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 DMSO, DMF, ethanol, and 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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC40411

QC Data

View QC data: current batch, Lot#SSC40411

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SSR128129E is a FGFR inhibitor with an IC50 of 1.9 μM for FGFR1.

In vitro activity:

SSR12819E radiosensitised radioresistant U87 and SF763 glioblastoma cells. 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://pubmed.ncbi.nlm.nih.gov/24953334/

In vivo activity:

SSR128129E may be a promising drug candidate for the prevention of obesity via suppressing adipogenesis. SSR128129E administration significantly reduced the body weight gain and the fat content of mice. SSR128129E did not increase, but decreased the thermogenic capability of both brown and white fat. However, SSR128129E markedly suppressed adipogenesis of adipose tissues. Reference: Mol Biol Rep. 2022 Sep;49(9):8641-8649. https://pubmed.ncbi.nlm.nih.gov/35731366/

	Solvent	mg/mL	mM
Solubility
	DMSO	51.0	157.25
	DMF	30.0	92.50
	Ethanol	1.0	3.08
	Water	1.0	3.08
	PBS (pH 7.2)	1.0	3.08

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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. 2. Zhang X, Wen X, Hu G, Zhang Q, Sun Q, Jia Y, Liu Y, Lin H, Li H. The fibroblast growth factor receptor antagonist SSR128129E inhibits fat accumulation via suppressing adipogenesis in mice. Mol Biol Rep. 2022 Sep;49(9):8641-8649. doi: 10.1007/s11033-022-07699-1. Epub 2022 Jun 22. PMID: 35731366. 3. 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. PMID: 23597562.

In vitro protocol:

In vivo protocol:

1. Zhang X, Wen X, Hu G, Zhang Q, Sun Q, Jia Y, Liu Y, Lin H, Li H. The fibroblast growth factor receptor antagonist SSR128129E inhibits fat accumulation via suppressing adipogenesis in mice. Mol Biol Rep. 2022 Sep;49(9):8641-8649. doi: 10.1007/s11033-022-07699-1. Epub 2022 Jun 22. PMID: 35731366. 2. 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. PMID: 23597562.

1: 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. doi: 10.1016/j.abb.2012.05.020. Epub ahead of print. PMID: 22683470. 2: 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. PMID: 23597562. 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. Erratum in: Cancer Cell. 2016 Jul 11;30(1):176-178. doi: 10.1016/j.ccell.2016.06.015. PMID: 23597563. 4: Herbert C, Alcouffe C, Bono F. Première caractérisation d'un inhibiteur allostérique des récepteurs des fibroblast growth factors [SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling]. Med Sci (Paris). 2013 Oct;29(10):834-6. French. doi: 10.1051/medsci/20132910007. Epub 2013 Oct 18. PMID: 24148118. 5: 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. PMID: 24224032; PMCID: PMC3817113. 6: Fons P, Gueguen-Dorbes G, Herault JP, Geronimi F, Tuyaret J, Frédérique D, Schaeffer P, Volle-Challier C, Herbert JM, Bono F. Tumor vasculature is regulated by FGF/FGFR signaling-mediated angiogenesis and bone marrow-derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs. J Cell Physiol. 2015 Jan;230(1):43-51. doi: 10.1002/jcp.24656. PMID: 24760775. 7: 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. 8: De Smet F, Tembuyser B, Lenard A, Claes F, Zhang J, Michielsen C, Van Schepdael A, Herbert JM, Bono F, Affolter M, Dewerchin M, Carmeliet P. Fibroblast growth factor signaling affects vascular outgrowth and is required for the maintenance of blood vessel integrity. Chem Biol. 2014 Oct 23;21(10):1310-1317. doi: 10.1016/j.chembiol.2014.07.018. Epub 2014 Sep 4. PMID: 25200605. 9: 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. 2016 Jul 11;30(1):176-178. doi: 10.1016/j.ccell.2016.06.015. Epub 2016 Jul 11. Erratum for: Cancer Cell. 2013 Apr 15;23(4):489-501. doi: 10.1016/j.ccr.2013.02.018. PMID: 27479031. 10: Kappert F, Sreeramulu S, Jonker HRA, Richter C, Rogov VV, Proschak E, Hargittay B, Saxena K, Schwalbe H. Structural Characterization of the Interaction of the Fibroblast Growth Factor Receptor with a Small Molecule Allosteric Inhibitor. Chemistry. 2018 Jun 4;24(31):7861-7865. doi: 10.1002/chem.201801770. Epub 2018 May 3. PMID: 29656465. 11: Zhang X, Wen X, Hu G, Zhang Q, Sun Q, Jia Y, Liu Y, Lin H, Li H. The fibroblast growth factor receptor antagonist SSR128129E inhibits fat accumulation via suppressing adipogenesis in mice. Mol Biol Rep. 2022 Sep;49(9):8641-8649. doi: 10.1007/s11033-022-07699-1. Epub 2022 Jun 22. PMID: 35731366. 12: Wen X, Hu G, Xiao X, Zhang X, Zhang Q, Guo H, Li X, Liu Q, Li H. FGF2 positively regulates osteoclastogenesis via activating the ERK-CREB pathway. Arch Biochem Biophys. 2022 Sep 30;727:109348. doi: 10.1016/j.abb.2022.109348. Epub 2022 Jul 11. PMID: 35835230. 13: Mineev KS, Hargittay B, Jin J, Catapano C, Dietz MS, Segarra M, Harwardt MS, Richter C, Jonker HRA, Saxena K, Sreeramulu S, Heilemann M, Acker-Palmer A, Schwalbe H. Differential effects of the N-terminal helix of FGF8b on the activity of a small-molecule FGFR inhibitor in cell culture and for the extracellular domain of FGFR3c in solution. FEBS Lett. 2024 Oct;598(20):2518-2532. doi: 10.1002/1873-3468.14976. Epub 2024 Jul 12. PMID: 38997225.