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protein tyrosine phosphatase non-receptor type 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2976

Nomenclature: protein tyrosine phosphatase non-receptor type 1

Abbreviated Name: PTP1B

Family: Protein tyrosine phosphatases non-receptor type (PTPN)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 435 20q13.13 PTPN1 protein tyrosine phosphatase non-receptor type 1 2
Mouse - 432 2 H3 Ptpn1 protein tyrosine phosphatase, non-receptor type 1
Rat - 432 3q42 Ptpn1 protein tyrosine phosphatase, non-receptor type 1
Gene and Protein Information Comments
A second isoform from the human gene with a shorter N-terminus has been detected (RefSeq NP_001265547).
Previous and Unofficial Names Click here for help
protein tyrosine phosphatase | protein tyrosine phosphatase, non-receptor type 1 | PTP1B
Database Links Click here for help
Alphafold P18031 (Hs), P35821 (Mm), P20417 (Rn)
BRENDA 3.1.3.48
ChEMBL Target CHEMBL335 (Hs), CHEMBL3336 (Mm), CHEMBL2371 (Rn)
Ensembl Gene ENSG00000196396 (Hs), ENSMUSG00000027540 (Mm), ENSRNOG00000010574 (Rn)
Entrez Gene 5770 (Hs), 19246 (Mm), 24697 (Rn)
Human Protein Atlas ENSG00000196396 (Hs)
KEGG Enzyme 3.1.3.48
KEGG Gene hsa:5770 (Hs), mmu:19246 (Mm), rno:24697 (Rn)
OMIM 176885 (Hs)
Pharos P18031 (Hs)
RefSeq Nucleotide NM_002827 (Hs), NM_011201 (Mm), NM_012637 (Rn)
RefSeq Protein NP_002818 (Hs), NP_035331 (Mm), NP_036769 (Rn)
UniProtKB P18031 (Hs), P35821 (Mm), P20417 (Rn)
Wikipedia PTPN1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  PTP1B (PTPN1) in complex with 182
PDB Id:  8SKL
Ligand:  compound 182 [PMID: 37500611]
Resolution:  1.55Å
Species:  Human
References:  7
Enzyme Reaction Click here for help
EC Number: 3.1.3.48
Description Reaction Reference
Dephosphorylates O-phosphotyrosine groups in phosphoproteins. Protein tyrosine phosphate + H2O <=> protein tyrosine + phosphate

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 182 [PMID: 37500611] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.5 pKi 7
⤷ pKi 9.5 (Ki 3.4x10-10 M) [7]
(+)-4 enantiomer [PMID: 39046805] Small molecule or natural product Hs Inhibition 8.6 pKi 10
⤷ pKi 8.6 (Ki 2.7x10-9 M) [10]
NC1 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.1 pKi 6
⤷ pKi 5.1 (Ki 8x10-6 M) [6]
compound 182 [PMID: 37500611] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.2 pIC50 7
⤷ pIC50 9.2 (IC50 6.3x10-10 M) [7]
(+)-4 enantiomer [PMID: 39046805] Small molecule or natural product Hs Inhibition 9.1 pIC50 10
⤷ pIC50 9.1 (IC50 9x10-10 M) [10]
tegeprotafib Small molecule or natural product Hs Inhibition 8.0 – 9.0 pIC50 3
⤷ pIC50 8.0 – 9.0 (IC50 1x10-8 – 1x10-9 M) [3]
Description: Determined in a mobility shift assays using a phosphorylated insulin receptor peptide as substrate to measure inhibition of PTPN1-mediated dephopshorylation
HPN Small molecule or natural product Primary target of this compound Hs Inhibition 6.2 pIC50 12
⤷ pIC50 6.2 (IC50 6.3x10-7 M) [12]
Description: In a surface plasmon resonance (SPR) assay using immobilised recombinant enzyme PTP1B1–321.
trodusquemine Small molecule or natural product Hs Inhibition 6.0 pIC50 5
⤷ pIC50 6.0 (IC50 1x10-6 M) [5]
Description: In a cell-free assay using recombinant enzyme.
compound 7b [Haftchenary et al., 2013] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.3 pIC50 4
⤷ pIC50 5.3 (IC50 4.9x10-6 M) [4]
chlorogenic acid Small molecule or natural product Hs Inhibition 5.0 pIC50 11
⤷ pIC50 5.0 (IC50 1.1x10-5 M) [11]
I-C11 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 4.9 pIC50 14
⤷ pIC50 4.9 (IC50 1.18x10-5 M) [14]
Immunopharmacology Comments
Inhibition of PTPN1/2 promotes T cell-mediated anti-tumour immunity [1,7,15].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
General Comments
PTPN1 (a.k.a. PTP1B) is a non-receptor protein tyrosine phosphatase. It negatively regulates insulin signalling by dephosphorylating the phosphotryosine residues on the insulin receptor. It is a potential drug target for the treatment of type 2 diabetes (insulin resistance) [8]. PTPN1 inhibitors have been reported to have hypoglycaemic and other anti-diabetic effects [9,13].

References

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1. Baumgartner CK, Ebrahimi-Nik H, Iracheta-Vellve A, Hamel KM, Olander KE, Davis TGR, McGuire KA, Halvorsen GT, Avila OI, Patel CH et al.. (2023) The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature, 622 (7984): 850-862. [PMID:37794185]

2. Brown-Shimer S, Johnson KA, Lawrence JB, Johnson C, Bruskin A, Green NR, Hill DE. (1990) Molecular cloning and chromosome mapping of the human gene encoding protein phosphotyrosyl phosphatase 1B. Proc Natl Acad Sci USA, 87 (13): 5148-52. [PMID:2164224]

3. Farney EP, Shiroodi RK, Xiong Z, Zhang Q, O'connor M, Halvorsen GT, Zhao H, Baumgartner C, Frost JM, Kym PR et al.. (2021) Protein tyrosine phosphatase inhibitors and methods of use thereof. Patent number: WO2021127499A1. Assignee: Calico Life Sciences Llc, Abbvie Inc.. Priority date: 18/12/2020. Publication date: 24/06/2021.

4. Haftchenary S, Ball DP, Aubry I, Landry M, Shahani VM, Fletcher S, Page BDG, Jouk AO, Tremblay ML, Gunning PT. (2013) Identification of a potent salicylic acid-based inhibitor of tyrosine phosphatase PTP1B. Medchemcomm, (4): 987-992.

5. Lantz KA, Hart SG, Planey SL, Roitman MF, Ruiz-White IA, Wolfe HR, McLane MP. (2010) Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring), 18 (8): 1516-23. [PMID:20075852]

6. Li K, Hou X, Li R, Bi W, Yang F, Chen X, Xiao P, Liu T, Lu T, Zhou Y et al.. (2019) Identification and structure-function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22. J Biol Chem, 294 (21): 8653-8663. [PMID:30979725]

7. Liang S, Tran E, Du X, Dong J, Sudholz H, Chen H, Qu Z, Huntington ND, Babon JJ, Kershaw NJ et al.. (2023) A small molecule inhibitor of PTP1B and PTPN2 enhances T cell anti-tumor immunity. Nat Commun, 14 (1): 4524. [PMID:37500611]

8. Liu G, Trevillyan JM. (2002) Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr Opin Investig Drugs, 3 (11): 1608-16. [PMID:12476961]

9. Luo J, Xu Q, Jiang B, Zhang R, Jia X, Li X, Wang L, Guo C, Wu N, Shi D. (2018) Selectivity, cell permeability and oral availability studies of novel bromophenol derivative HPN as protein tyrosine phosphatase 1B inhibitor. Br J Pharmacol, 175 (1): 140-153. [PMID:29059712]

10. Mai VH, Ponce-Zea JE, Doan TP, Vu QH, Ryu B, Lee CH, Oh WK. (2024) Chalcone-Monoterpene Derivatives from the Buds of Cleistocalyx operculatus and Their Potential as Protein Tyrosine Phosphatase 1B Inhibitors. J Nat Prod, 87 (8): 1903-1913. [PMID:39046805]

11. Sánchez-Alonso P, Griera M, García-Marín J, Rodríguez-Puyol M, Alajarín R, Vaquero JJ, Rodríguez-Puyol D. (2021) Pyrrolo[1,2-a]quinoxal-5-inium salts and 4,5-dihydropyrrolo[1,2-a]quinoxalines: Synthesis, activity and computational docking for protein tyrosine phosphatase 1B. Bioorg Med Chem, 44: 116295. [PMID:34246920]

12. Shi D, Guo S, Jiang B, Guo C, Wang T, Zhang L, Li J. (2013) HPN, a synthetic analogue of bromophenol from red alga Rhodomela confervoides: synthesis and anti-diabetic effects in C57BL/KsJ-db/db mice. Mar Drugs, 11 (2): 350-62. [PMID:23364683]

13. Taylor SD, Hill B. (2004) Recent advances in protein tyrosine phosphatase 1B inhibitors. Expert Opin Investig Drugs, 13 (3): 199-214. [PMID:15013940]

14. Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. (2007) Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci USA, 104 (50): 19767-72. [PMID:18056643]

15. (2023) A Dual PTPN2/PTPN1 Active-Site Inhibitor Promotes Antitumor Immunity. Cancer Discov,: OF1 [Epub ahead of print]. [PMID:37861299]

How to cite this page

Protein tyrosine phosphatases non-receptor type (PTPN): protein tyrosine phosphatase non-receptor type 1. Last modified on 11/09/2024. Accessed on 14/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2976.