NSC-87877 | CAS#56990-57-9 | SHP-1 and SHP-2 inhibitor

MedKoo Cat#: 406795 | Name: NSC-87877 free acid

Description:

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

NSC-87877 is a cell-permeable, inhibitor of both SHP-1 and SHP-2 (IC50 = 355 and 318 nM, respectively). NSC-87877 shows effective growth inhibition and induction of apoptosis in NB cell lines. In an intrarenal mouse model of NB, NSC-87877 treatment results in decreased tumor growth and increased p53 and p38 activity. DUSP26 inhibition with NSC-87877 is an effective strategy to induce NB cell cytotoxicity in vitro and in vivo through activation of the p53 and p38 mitogen-activated protein kinase (MAPK) tumor-suppressor pathways.

Chemical Structure

NSC-87877 free acid

CAS#56990-57-9 (free acid)

Theoretical Analysis

MedKoo Cat#: 406795

Name: NSC-87877 free acid

CAS#: 56990-57-9 (free acid)

Chemical Formula: C19H13N3O7S2

Exact Mass: 459.0195

Molecular Weight: 459.45

Elemental Analysis: C, 49.67; H, 2.85; N, 9.15; O, 24.38; S, 13.96

Price and Availability

Size	Price	Availability
25mg	USD 350.00	2 Weeks
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks

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Related CAS #

56990-57-9 (free acid) 56932-43-5 (sodium)

Synonym

NSC-87877; NSC87877; NSC87877.

IUPAC/Chemical Name

(E)-8-hydroxy-7-((6-sulfonaphthalen-2-yl)diazenyl)quinoline-5-sulfonic acid

InChi Key

XGMFVZOKHBRUTL-QURGRASLSA-N

InChi Code

InChI=1S/C19H13N3O7S2/c23-19-16(10-17(31(27,28)29)15-2-1-7-20-18(15)19)22-21-13-5-3-12-9-14(30(24,25)26)6-4-11(12)8-13/h1-10,23H,(H,24,25,26)(H,27,28,29)/b22-21+

SMILES Code

OS(C(C=C1)=CC(C1=C2)=CC=C2/N=N/C3=C(O)C4=NC=CC=C4C(S(O)(=O)=O)=C3)(=O)=O

Appearance

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

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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

Instruction

View handling instruction

Biological target:

NSC-87877 is a potent inhibitor of Shp2 and Shp1 protein tyrosine phosphatases (SH-PTP2 and SH-PTP1), with IC50 values of 0.318 μM, 0.355 μM shp2 and shp1.

In vitro activity:

NSC-87877 cross-inhibited Shp1 in vitro, but it was selective for Shp2 over other PTPs (PTP1B, HePTP, DEP1, CD45, and LAR). It is noteworthy that NSC-87877 inhibited epidermal growth factor (EGF)-induced activation of Shp2 PTP, Ras, and Erk1/2 in cell cultures but did not block EGF-induced Gab1 tyrosine phosphorylation or Gab1-Shp2 association. Furthermore, NSC-87877 inhibited Erk1/2 activation by a Gab1-Shp2 chimera but did not affect the Shp2-independent Erk1/2 activation by phorbol 12-myristate 13-acetate. Reference: Mol Pharmacol. 2006 Aug;70(2):562-70. https://pubmed.ncbi.nlm.nih.gov/16717135/

In vivo activity:

In order to test the effect of small molecule inhibition of DUSP26 in vivo, this study used a well-established intrarenal NB tumor mouse model. The control group tumors were significantly larger than the NSC-87877-treated group (P<0.01; Figure 7b). Tumor samples harvested after 15 days of NSC-87877 treatment from the experiment in Figure 7a were tested for PARP and caspase-7 cleavage to show presence of cellular apoptosis in vivo. In two of the experimental samples, this study saw more PARP and caspase-7 cleavage when compared with the control sample (Figure 7d). In summary, this study demonstrated a significant decrease in tumor growth in NSC-87877-treated mice and showed a similar mechanism of p53 and p38 activation resulting in cellular apoptosis. Reference: Cell Death Dis. 2015 Aug 6;6(8):e1841. https://pubmed.ncbi.nlm.nih.gov/26247726/

	Solvent	mg/mL	mM
Solubility
	DMSO	9.3	20.21
	PBS (pH 7.2)	0.5	1.09
	Water	23.4	50.91

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 459.45 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. Song M, Park JE, Park SG, Lee DH, Choi HK, Park BC, Ryu SE, Kim JH, Cho S. NSC-87877, inhibitor of SHP-1/2 PTPs, inhibits dual-specificity phosphatase 26 (DUSP26). Biochem Biophys Res Commun. 2009 Apr 17;381(4):491-5. doi: 10.1016/j.bbrc.2009.02.069. Epub 2009 Feb 20. PMID: 19233143. 2. Chen L, Sung SS, Yip ML, Lawrence HR, Ren Y, Guida WC, Sebti SM, Lawrence NJ, Wu J. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol. 2006 Aug;70(2):562-70. doi: 10.1124/mol.106.025536. Epub 2006 May 22. PMID: 16717135. 3. Shi Y, Ma IT, Patel RH, Shang X, Chen Z, Zhao Y, Cheng J, Fan Y, Rojas Y, Barbieri E, Chen Z, Yu Y, Jin J, Kim ES, Shohet JM, Vasudevan SA, Yang J. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015 Aug 6;6(8):e1841. doi: 10.1038/cddis.2015.207. PMID: 26247726; PMCID: PMC4558500.

In vitro protocol:

In vivo protocol:

1. Shi Y, Ma IT, Patel RH, Shang X, Chen Z, Zhao Y, Cheng J, Fan Y, Rojas Y, Barbieri E, Chen Z, Yu Y, Jin J, Kim ES, Shohet JM, Vasudevan SA, Yang J. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015 Aug 6;6(8):e1841. doi: 10.1038/cddis.2015.207. PMID: 26247726; PMCID: PMC4558500.

1: Jung S, Nah J, Han J, Choi SG, Kim H, Park J, Pyo HK, Jung YK. Dual-specificity phosphatase 26 (DUSP26) stimulates Aβ42 generation by promoting amyloid precursor protein axonal transport during hypoxia. J Neurochem. 2016 Jun;137(5):770-81. doi: 10.1111/jnc.13597. Epub 2016 Mar 17. PubMed PMID: 26924229. 2: Shi Y, Ma IT, Patel RH, Shang X, Chen Z, Zhao Y, Cheng J, Fan Y, Rojas Y, Barbieri E, Chen Z, Yu Y, Jin J, Kim ES, Shohet JM, Vasudevan SA, Yang J. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015 Aug 6;6:e1841. doi: 10.1038/cddis.2015.207. PubMed PMID: 26247726; PubMed Central PMCID: PMC4558500. 3: Zhou RP, Deng MT, Chen LY, Fang N, Du C, Chen LP, Zou YQ, Dai JH, Zhu ML, Wang W, Lin SJ, Liu RH, Luo J. Shp2 regulates chlorogenic acid-induced proliferation and adipogenic differentiation of bone marrow-derived mesenchymal stem cells in adipogenesis. Mol Med Rep. 2015 Jun;11(6):4489-95. doi: 10.3892/mmr.2015.3285. Epub 2015 Jan 30. PubMed PMID: 25634525. 4: Ding X, Cai J, Li S, Liu XD, Wan Y, Xing GG. BDNF contributes to the development of neuropathic pain by induction of spinal long-term potentiation via SHP2 associated GluN2B-containing NMDA receptors activation in rats with spinal nerve ligation. Neurobiol Dis. 2015 Jan;73:428-51. doi: 10.1016/j.nbd.2014.10.025. Epub 2014 Nov 8. PubMed PMID: 25447233. 5: Chang YF, Hsu YF, Chiu PT, Huang WJ, Huang SW, Ou G, Sheu JR, Hsu MJ. WMJ-S-001, a novel aliphatic hydroxamate derivative, exhibits anti-angiogenic activities via Src-homology-2-domain-containing protein tyrosine phosphatase 1. Oncotarget. 2015 Jan 1;6(1):85-100. PubMed PMID: 25415226; PubMed Central PMCID: PMC4381580. 6: Lee KA, Bae EA, Song YC, Kim EK, Lee YS, Kim TG, Kang CY. A multimeric carcinoembryonic antigen signal inhibits the activation of human T cells by a SHP-independent mechanism: a potential mechanism for tumor-mediated suppression of T-cell immunity. Int J Cancer. 2015 Jun 1;136(11):2579-87. doi: 10.1002/ijc.29314. Epub 2014 Nov 21. PubMed PMID: 25379865. 7: Pinzon-Guzman C, Xing T, Zhang SS, Barnstable CJ. Regulation of rod photoreceptor differentiation by STAT3 is controlled by a tyrosine phosphatase. J Mol Neurosci. 2015 Jan;55(1):152-9. doi: 10.1007/s12031-014-0397-1. Epub 2014 Aug 10. PubMed PMID: 25108518; PubMed Central PMCID: PMC4293205. 8: Luo Q, Sun Y, Gong FY, Liu W, Zheng W, Shen Y, Hua ZC, Xu Q. Blocking initial infiltration of pioneer CD8(+) T-cells into the CNS via inhibition of SHP-2 ameliorates experimental autoimmune encephalomyelitis in mice. Br J Pharmacol. 2014 Apr;171(7):1706-21. doi: 10.1111/bph.12565. PubMed PMID: 24372081; PubMed Central PMCID: PMC3966750. 9: Gan Y, Zhang Y, Buckels A, Paterson AJ, Jiang J, Clemens TL, Zhang ZY, Du K, Chang Y, Frank SJ. IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine phosphatase activity. Mol Endocrinol. 2013 Nov;27(11):1969-79. doi: 10.1210/me.2013-1178. Epub 2013 Sep 12. PubMed PMID: 24030252; PubMed Central PMCID: PMC3805849. 10: Craig J, Mikhailenko I, Noyes N, Migliorini M, Strickland DK. The LDL receptor-related protein 1 (LRP1) regulates the PDGF signaling pathway by binding the protein phosphatase SHP-2 and modulating SHP-2- mediated PDGF signaling events. PLoS One. 2013 Jul 26;8(7):e70432. doi: 10.1371/journal.pone.0070432. Print 2013. PubMed PMID: 23922991; PubMed Central PMCID: PMC3724782. 11: Tanaka T, Fujita Y, Ueno M, Shultz LD, Yamashita T. Suppression of SHP-1 promotes corticospinal tract sprouting and functional recovery after brain injury. Cell Death Dis. 2013 Apr 4;4:e567. doi: 10.1038/cddis.2013.102. PubMed PMID: 23559001; PubMed Central PMCID: PMC3641325. 12: Fraineau S, Monvoisin A, Clarhaut J, Talbot J, Simonneau C, Kanthou C, Kanse SM, Philippe M, Benzakour O. The vitamin K-dependent anticoagulant factor, protein S, inhibits multiple VEGF-A-induced angiogenesis events in a Mer- and SHP2-dependent manner. Blood. 2012 Dec 13;120(25):5073-83. doi: 10.1182/blood-2012-05-429183. Epub 2012 Oct 12. PubMed PMID: 23065156. 13: Peng H, Carretero OA, Peterson EL, Yang XP, Santra K, Rhaleb NE. N-Acetyl-seryl-aspartyl-lysyl-proline inhibits ET-1-induced collagen production by preserving Src homology 2-containing protein tyrosine phosphatase-2 activity in cardiac fibroblasts. Pflugers Arch. 2012 Oct;464(4):415-23. Epub 2012 Sep 12. PubMed PMID: 22968858; PubMed Central PMCID: PMC3459332. 14: Wu X, Guo W, Wu L, Gu Y, Gu L, Xu S, Wu X, Shen Y, Ke Y, Tan R, Sun Y, Xu Q. Selective sequestration of STAT1 in the cytoplasm via phosphorylated SHP-2 ameliorates murine experimental colitis. J Immunol. 2012 Oct 1;189(7):3497-507. Epub 2012 Aug 31. PubMed PMID: 22942432. 15: Stephan MT, Stephan SB, Bak P, Chen J, Irvine DJ. Synapse-directed delivery of immunomodulators using T-cell-conjugated nanoparticles. Biomaterials. 2012 Aug;33(23):5776-87. doi: 10.1016/j.biomaterials.2012.04.029. Epub 2012 May 15. PubMed PMID: 22594972; PubMed Central PMCID: PMC3395588. 16: Wang G, Jin C, Hou Y, Zhang L, Li S, Zhang L, Wu B, Li Q, Xu C, Tian Y, Zhang L. Overexpression of Shp-2 attenuates apoptosis in neonatal rat cardiac myocytes through the ERK pathway. Exp Mol Pathol. 2012 Aug;93(1):50-5. doi: 10.1016/j.yexmp.2012.04.005. Epub 2012 Apr 16. PubMed PMID: 22537548. 17: Peng HY, Chen GD, Lai CY, Hsieh MC, Lin TB. Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats. Pain. 2012 May;153(5):1042-53. doi: 10.1016/j.pain.2012.02.006. Epub 2012 Mar 17. PubMed PMID: 22425446. 18: Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F. Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4. J Lipid Res. 2011 Nov;52(11):1936-48. doi: 10.1194/jlr.M015552. Epub 2011 Sep 8. PubMed PMID: 21903867; PubMed Central PMCID: PMC3196225. 19: Ketroussi F, Giuliani M, Bahri R, Azzarone B, Charpentier B, Durrbach A. Lymphocyte cell-cycle inhibition by HLA-G is mediated by phosphatase SHP-2 and acts on the mTOR pathway. PLoS One. 2011;6(8):e22776. doi: 10.1371/journal.pone.0022776. Epub 2011 Aug 24. PubMed PMID: 21887223; PubMed Central PMCID: PMC3160837. 20: Won KJ, Lee HM, Lee CK, Lin HY, Na H, Lim KW, Roh HY, Sim S, Song H, Choi WS, Lee SH, Kim B. Protein tyrosine phosphatase SHP-2 is positively involved in platelet-derived growth factor-signaling in vascular neointima formation via the reactive oxygen species-related pathway. J Pharmacol Sci. 2011;115(2):164-75. PubMed PMID: 21343667.