Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	593	12q24.13	PTPN11	protein tyrosine phosphatase non-receptor type 11

Previous and Unofficial Names

Noonan syndrome 1 (NS1) | SH2 domain-containing protein tyrosine phosphatase 2 | SHP-2 | src homology region 2 domain phosphatase | Src homology-2 domain-containing phosphatase Shp2

Database Links
Alphafold	Q06124 (Hs)
BRENDA	3.1.3.48
ChEMBL Target	CHEMBL3864 (Hs)
Ensembl Gene	ENSG00000179295 (Hs)
Entrez Gene	5781 (Hs)
Human Protein Atlas	ENSG00000179295 (Hs)
KEGG Enzyme	3.1.3.48
KEGG Gene	hsa:5781 (Hs)
OMIM	176876 (Hs)
Pharos	Q06124 (Hs)
UniProtKB	Q06124 (Hs)
Wikipedia	PTPN11 (Hs)

Enzyme Reaction
EC Number: 3.1.3.48

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference batoprotafib Hs Inhibition 8.0 pIC50 3 ⤷ pIC50 8.0 (IC50 1.1x10-8 M) [3] vociprotafib Hs Inhibition - - 2 ⤷ [2]
Inhibitor Comments
Other SHP2 inhibitors (whose structures have not yet been disclosed) include BBP-398 (formerly IACS-15509; Navire Pharma; phase 1) and JAB-3312 (Jacobio Pharmaceuticals; phase 1/2).

Allosteric Modulators
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference migoprotafib Hs Inhibition >6.8 – 9.0 pIC50 5 ⤷ pIC50 >9.0 (IC50 <1x10-9 M) [5] Description: Measuring dephosphorylation catalysed by wild type SHP2 in a biochemical assay pIC50 6.8 (IC50 1.7x10-7 M) [5] Description: Measuring dephosphorylation catalysed by SHP2E76K in a biochemical assay

Immunopharmacology Comments

SHP2 regulates programmed cell death 1 (PD-1)-mediated signal transduction and it is therefore involved in immune checkpoint modulation.

Immuno Process Associations

Immuno Process:  Cellular signalling GO Annotations:  Associated to 3 GO processes GO:0031295 T cell costimulation TAS GO:0042130 negative regulation of T cell proliferation IDA GO:1902564 negative regulation of neutrophil activation IDA

Immuno Process:  Chemotaxis & migration GO Annotations:  Associated to 2 GO processes GO:0031295 T cell costimulation TAS GO:0042130 negative regulation of T cell proliferation IDA

Immuno Process:  Cytokine production & signalling GO Annotations:  Associated to 5 GO processes GO:0019221 cytokine-mediated signaling pathway TAS GO:0032480 negative regulation of type I interferon production IDA GO:0032728 positive regulation of interferon-beta production ISS GO:0032760 positive regulation of tumor necrosis factor production ISS GO:0060338 regulation of type I interferon-mediated signaling pathway TAS

Immuno Process:  Immune regulation GO Annotations:  Associated to 4 GO processes GO:0031295 T cell costimulation TAS GO:0042130 negative regulation of T cell proliferation IDA GO:0060338 regulation of type I interferon-mediated signaling pathway TAS GO:1902564 negative regulation of neutrophil activation IDA

Immuno Process:  Inflammation GO Annotations:  Associated to 2 GO processes GO:0060338 regulation of type I interferon-mediated signaling pathway TAS GO:1902564 negative regulation of neutrophil activation IDA

Immuno Process:  T cell (activation) GO Annotations:  Associated to 2 GO processes GO:0031295 T cell costimulation TAS GO:0042130 negative regulation of T cell proliferation IDA

General Comments

Src homology-2 domain-containing phosphatase SHP2 is encoded by the PTPN11 gene. It is a cytosolic protein-tyrosine phosphatase whose activity opposes the action of protein kinases that phosphorylate tyrosine residues on receptors for growth factors and cytokines [1]. SHP2 promotes activation of the RAS-MAPK-ERK signalling pathway and it participates in the PD-1/PD-L1 pathway that regulates immune surveillance. It represents a potential new target for the treatment of cancer [4] and other human diseases that are 1) driven by gain-of-function mutations and/or over-expression of receptor tyrosine kinases, or 2) the result of mutations in PTPN11 that have been identified in certain cancers and congenital disorders. Mutations in PTPN11 cause Noonan syndrome 1 and LEOPARD syndrome. Small molecule SHP2 inhibitors are being investigated for clinical applications, primarily to block dysregulated RAS-MAPK-ERK signalling in advanced solid tumours, and also for potential to enhance the efficacy of anti-PD-1/PD-L1-based immunotherapies, RTK inhibitors or direct KRAS inhibitors.