NSC-87877 disodium

NSC-87877 disodium 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, respectively[1]. NSC-87877 also inhibits dual-specificity phosphatase 26 (DUSP26)[2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase

IC50: 0.318 μM (shp2), 0.355 μM (shp1)[1].

NSC-87877 (0-0.5 μM, 5 days) inhibits DUSP26 function in NB cell lines[3]. NSC-87877 (0-0.5 μM, 5 days) results in increased p53 phosphorylation (Ser37 and Ser46) and activation[3]. Cell Viability Assay[2] Cell Line: p53 wild-type neuroblastoma (NB) cell lines. Concentration: 0, 0.25, 0.5 μM. Incubation Time: 5 days. Result: Resulted in increased p53 phosphorylation (Ser37 and Ser46) and activation, increased activation of downstream p38 effector proteins (heat shock protein 27 (HSP27) and MAP kinase-activated protein kinase 2 (MAPKAPK2)) and poly ADP ribose polymerase/caspase-3 cleavage. Inhibited DUSP26 function in NB cell lines. Resulted in apoptosis in many cell lines at varying IC50 levels of 1.84 μM (IMR32), 6.35 μM (SK-N-SH), 8.69 μM (NB-19), 12.6 μM (SMS-KCN), 15.7 μM (SH-SY5Y), 15.8 μM (JF) and 19.0 μM (CHLA-225), respectively.

NSC-87877 (30 mg/kg, IP once daily for 15 days) possesses excellent anti- neuroblastoma activity[3]. Animal Model: Intrarenal neuroblastoma (NB) tumor mouse model in female nude mice[3]. Dosage: 30 mg/kg. Administration: IP once daily for 15 days. Result: Significantly inhibited NB tumor growth.

[1]. Chen L, et al. Discovery of a novel shp2 protein tyrosine phosphatase inhibitor. Mol Pharmacol. 2006 Aug;70(2):562-70.

[2]. Song M, et al. 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.

[3]. Y Shi, et al. NSC-87877 inhibits DUSP26 function in neuroblastoma resulting in p53-mediated apoptosis. Cell Death Dis. 2015 Aug 6;6(8):e1841.