Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors

Tyrosine Phosphatase ◽

Receptor Protein ◽

Ptpn11 Gene ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Receptor Protein Tyrosine Phosphatase ◽

Src Homology ◽

Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) is a non-receptor protein tyrosine phosphatase encoded by the Ptpn11 gene, which regulates cell growth, differentiation and apoptosis via modulating various signaling...

Investigating the reason for loss-of-function of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) caused by Y279C mutation through molecular dynamics simulation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2019.1634641 ◽

2019 ◽

Vol 38 (9) ◽

pp. 2509-2520 ◽

Cited By ~ 2

Author(s):

Wen-Shan Liu ◽

Rui-Rui Wang ◽

Wei-Ya Li ◽

Mei Rong ◽

Chi-Lu Liu ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Tyrosine Phosphatase ◽

Dynamics Simulation ◽

Loss Of Function ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Synthesis and biological evaluation of 2,5-diaryl-1,3,4-oxadiazole derivatives as novel Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) inhibitors

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.105384 ◽

2021 ◽

pp. 105384

Author(s):

Xiang-Dong Meng ◽

Li-Xin Gao ◽

Zhi-Jia Wang ◽

Bo Feng ◽

Chun Zhang ◽

...

Keyword(s):

Synthesis And Biological Evaluation

Tyrosine Phosphatase ◽

Biological Evaluation ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Oxadiazole Derivatives ◽

Src Homology 2 Domain ◽

Inhibition of Src homology 2 domain containing protein tyrosine phosphatase as the possible mechanism of metformin-assisted amelioration of obesity induced insulin resistance in high fat diet fed C57BL/6J mice

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.04.012 ◽

2017 ◽

Vol 487 (1) ◽

pp. 54-61 ◽

Cited By ~ 5

Author(s):

Yadhu Sharma ◽

Samina Bashir ◽

Ansarullah ◽

Mohemmed Faraz Khan ◽

Altaf Ahmad ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Tyrosine Phosphatase ◽

High Fat ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Chicken Ig-Like Receptor B2, a Member of a Multigene Family, Is Mainly Expressed on B Lymphocytes, Recruits Both Src Homology 2 Domain Containing Protein Tyrosine Phosphatase (SHP)-1 and SHP-2, and Inhibits Proliferation

The Journal of Immunology ◽

10.4049/jimmunol.173.12.7385 ◽

2004 ◽

Vol 173 (12) ◽

pp. 7385-7393 ◽

Cited By ~ 29

Author(s):

Birgit C. Viertlboeck ◽

Richard P. M. A. Crooijmans ◽

Martien A. M. Groenen ◽

Thomas W. F. Göbel

Keyword(s):

B Lymphocytes ◽

Multigene Family ◽

Tyrosine Phosphatase ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Cell surface expression of channel catfish leukocyte immune-type receptors (IpLITRs) and recruitment of both Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2

Developmental & Comparative Immunology ◽

10.1016/j.dci.2008.10.006 ◽

2009 ◽

Vol 33 (4) ◽

pp. 570-582 ◽

Cited By ~ 19

Author(s):

Benjamin C.S. Montgomery ◽

Jacqueline Mewes ◽

Chelsea Davidson ◽

Deborah N. Burshtyn ◽

James L. Stafford

Keyword(s):

Cell Surface ◽

Channel Catfish ◽

Tyrosine Phosphatase ◽

Surface Expression ◽

Cell Surface Expression ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Inhibitors of Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (Shp2) Based on Oxindole Scaffolds

Journal of Medicinal Chemistry ◽

10.1021/jm8002526 ◽

2008 ◽

Vol 51 (16) ◽

pp. 4948-4956 ◽

Cited By ~ 55

Author(s):

Harshani R. Lawrence ◽

Roberta Pireddu ◽

Liwei Chen ◽

Yunting Luo ◽

Shen-Shu Sung ◽

...

Keyword(s):

Tyrosine Phosphatase ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

European Journal of Immunology ◽

10.1002/eji.200635864 ◽

2006 ◽

Vol 36 (12) ◽

pp. 3216-3226 ◽

Cited By ~ 16

Author(s):

Atsushi Fukunaga ◽

Hiroshi Nagai ◽

Xijun Yu ◽

Shuntaro Oniki ◽

Hideki Okazawa ◽

...

Keyword(s):

Tyrosine Phosphatase ◽

Langerhans Cell ◽

Cell Maturation ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain ◽

Phosphatase Substrate

Regulation of macrophage nitric oxide production by the protein tyrosine phosphatase Src homology 2 domain phosphotyrosine phosphatase 1 (SHP-1)

Immunology ◽

10.1111/j.1365-2567.2008.02929.x ◽

2008 ◽

Vol 127 (1) ◽

pp. 123-133 ◽

Cited By ~ 37

Author(s):

Julie Blanchette ◽

Issa Abu-Dayyeh ◽

Kasra Hassani ◽

Lorie Whitcombe ◽

Martin Olivier

Keyword(s):

Nitric Oxide ◽

Tyrosine Phosphatase ◽

Nitric Oxide Production ◽

Phosphotyrosine Phosphatase ◽

Protein Tyrosine ◽

Oxide Production ◽

Src Homology 2 ◽

Src Homology ◽

Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Promotes Inflammation and Accelerates Osteoarthritis by Activating β-Catenin

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.646386 ◽

2021 ◽

Vol 9 ◽

Author(s):

Tenghui Tao ◽

Danni Luo ◽

Chenghao Gao ◽

Hui Liu ◽

Zehua Lei ◽

...

Keyword(s):

Tyrosine Phosphatase ◽

Cartilage Degradation ◽

Mitogen Activated Protein Kinase ◽

Osteophyte Formation ◽

Protein Tyrosine ◽

Src Homology 2 ◽

Primary Mouse ◽

Src Homology ◽

Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation, subchondral bone remodeling and osteophyte formation. Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) has not been fully investigated in the pathogenesis of OA. In this study, we found that SHP2 expression was significantly increased after interleukin-1β (IL-1β) treatment in primary mouse chondrocytes. Inhibition of SHP2 using siRNA reduced MMP3, MMP13 levels, but increased AGGRECAN, COL2A1, SOX9 expression in vitro. On the contrary, overexpression of SHP2 exerted the opposite results and promoted cartilage degradation. Mechanistically, SHP2 activated Wnt/β-catenin signaling possibly through directly binding to β-catenin. SHP2 also induced inflammation through activating Mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways. Our in vivo studies showed that SHP2 knockdown effectively delayed cartilage destruction and reduced osteophyte formation in the mouse model of OA induced by destabilization of the medial meniscus (DMM). Altogether, our study identifies that SHP2 is a novel and potential therapeutic target of OA.