Discovery of a Novel Shp2 Protein Tyrosine Phosphatase Inhibitor

@article{Chen2006DiscoveryOA,
  title={Discovery of a Novel Shp2 Protein Tyrosine Phosphatase Inhibitor},
  author={Liwei Chen and Shen-Shu Sung and M. L. Richard Yip and Harshani R. Lawrence and Yuan Ren and Wayne C. Guida and Sa{\"i}d M. Sebti and Nicholas J. Lawrence and Jie Wu},
  journal={Molecular Pharmacology},
  year={2006},
  volume={70},
  pages={562 - 570}
}
Shp2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene. It is involved in growth factorinduced activation of mitogen-activated protein (MAP) kinases Erk1 and Erk2 (Erk1/2) and has been implicated in the pathogenicity of the oncogenic bacterium Helicobacter pylori. Moreover, gain-of-function Shp2 mutations have been found in childhood leukemias and Noonan syndrome. Thus, small molecule Shp2 PTP inhibitors are much needed reagents for evaluation of Shp2 as a… 
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TLDR
Evidence is provided that SHP2 is a “druggable” target for the treatment of PTPN11-associated diseases as the small-molecule SHP1 inhibitor identified has a simple chemical structure and represents an ideal lead compound for the development of novel anti-SHP2 drugs.
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Discovery of a Novel Inhibitor of the Protein Tyrosine Phosphatase Shp2
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Identification of a potent Shp2 inhibitor, Fumosorinone (Fumos) from entomogenous fungi, which shows selective inhibition of Shp 2 over other tested PTPs is described, suggesting that Fumo can inhibit Shp1-dependent cell signaling in human cells and has a potential for treatment of Sh p2-associated diseases.
Small Molecule Therapeutics Targeting Protein Tyrosine Phosphatase SHP 2 for the Treatment of PTPN 11-Associated Malignancies
TLDR
Evidence is provided that SHP2 is a "druggable" target for the treatment of PTPN11-associated diseases as the small-molecule SHP1 inhibitor identified has a simple chemical structure and represents an ideal lead compound for the development of novel anti-SHP2 drugs.
Fragment-based screening of the oncogenic protein tyrosine phosphatase SHP2
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Use of a fragment-based screening approach to accelerate the discovery of novel SHP2 inhibitors has enabled the identification of two novel and distinct chemical scaffolds, both of which now serve as validated chemical precursors for the development of more potentSHP2 lead inhibitors.
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The identification of an allosteric SHP2 inhibitor 1-(4-(6-bromonaphthalen- 2-yl)thiazol-2-yl)-4-methylpiperidin-4-amine (23) that locksSHP2 in a closed conformation by binding to the interface of the N-terminal SH2, C-terminals, and phosphatase domains is reported.
Medicinal chemistry strategies for the development of protein tyrosine phosphatase SHP2 inhibitors and PROTAC degraders.
NSC-87877, inhibitor of SHP-1/2 PTPs, inhibits dual-specificity phosphatase 26 (DUSP26).
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