Target General Infomation
Target ID
T89529
Former ID
TTDR01437
Target Name
mRNA of Protein tyrosine phosphatase-1B
Gene Name
PTPN1
Synonyms
mRNA of PTP-1B; mRNA of PTPN1; mRNA of Protein-tyrosine phosphatase 1B; mRNA of Tyrosine-protein phosphatase non-receptor type 1; PTPN1
Target Type
Successful
Disease Colour dead tissues [ICD code not available]
Infections [ICD9: 001-139; ICD10: A00-B99]
Type 2 diabetes [ICD9: 250; ICD10: E11]
Function
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.
BioChemical Class
Target of antisense drug
Target Validation
T89529
UniProt ID
EC Number
EC 3.1.3.48
Sequence
MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK
CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP
DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD
PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE
PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG
IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT
AGAYLCYRFLFNSNT
Structure
1A5Y; 1AAX; 1BZC; 1BZH; 1BZJ; 1C83; 1C84; 1C85; 1C86; 1C87; 1C88; 1ECV; 1EEN; 1EEO; 1G1F; 1G1G; 1G1H; 1G7F; 1G7G; 1GFY; 1I57; 1JF7; 1KAK; 1KAV; 1L8G; 1LQF; 1NL9; 1NNY; 1NO6; 1NWE; 1NWL; 1NZ7; 1OEM; 1OEO; 1OES; 1OET; 1OEU; 1OEV; 1ONY; 1ONZ; 1PA1; 1PH0; 1PTT; 1PTU; 1PTV; 1PTY; 1PXH; 1PYN; 1Q1M; 1Q6J; 1Q6M; 1Q6N; 1Q6P; 1Q6S; 1Q6T; 1QXK; 1SUG; 1T48; 1T49; 1T4J; 1WAX; 1XBO; 2AZR; 2B07; 2B4S; 2BGD; 2BGE; 2CM2; 2CM3; 2CM7; 2CM8; 2CMA; 2CMB; 2CMC; 2CNE; 2CNF; 2CNG; 2CNH; 2CNI; 2F6F; 2F6T; 2F6V; 2F6W; 2F6Y; 2F6Z; 2F70; 2F71; 2FJM; 2FJN; 2H4G; 2H4K; 2HB1; 2HNP; 2HNQ; 2NT7; 2NTA; 2QBP; 2QBQ; 2QBR; 2QBS; 2VEU; 2VEV; 2VEW; 2VEX; 2VEY; 2ZMM; 2ZN7; 3A5J; 3A5K; 3CWE; 3D9C; 3EAX; 3EB1; 3EU0; 3I7Z; 3I80; 3QKP; 3QKQ; 3SME; 3ZMP; 3ZMQ; 3ZV2; 4BJO; 4I8N; 4QAH; 4QBE; 1A5Y; 1AAX; 1BZC; 1BZH; 1BZJ; 1C83; 1C84; 1C85; 1C86; 1C87; 1C88; 1ECV; 1EEN; 1EEO; 1G1F; 1G1G; 1G1H; 1G7F; 1G7G; 1GFY; 1I57; 1JF7; 1KAK; 1KAV; 1L8G; 1LQF; 1NL9; 1NNY; 1NO6; 1NWE; 1NWL; 1NZ7; 1OEM; 1OEO; 1OES; 1OET; 1OEU; 1OEV; 1ONY; 1ONZ; 1PA1; 1PH0; 1PTT; 1PTU; 1PTV; 1PTY; 1PXH; 1PYN; 1Q1M; 1Q6J; 1Q6M; 1Q6N; 1Q6P; 1Q6S; 1Q6T; 1QXK; 1SUG; 1T48; 1T49; 1T4J; 1WAX; 1XBO; 2AZR; 2B07; 2B4S;2BGD; 2BGE; 2CM2; 2CM3; 2CM7; 2CM8; 2CMA; 2CMB; 2CMC; 2CNE; 2CNF; 2CNG; 2CNH; 2CNI; 2F6F; 2F6T; 2F6V; 2F6W; 2F6Y; 2F6Z; 2F70; 2F71; 2FJM; 2FJN; 2H4G; 2H4K; 2HB1; 2HNP; 2HNQ; 2NT7; 2NTA; 2QBP; 2QBQ; 2QBR; 2QBS; 2VEU; 2VEV; 2VEW; 2VEX; 2VEY; 2ZMM; 2ZN7; 3A5J; 3A5K; 3CWE; 3D9C; 3EAX; 3EB1; 3EU0; 3I7Z; 3I80; 3QKP; 3QKQ; 3SME; 3ZMP; 3ZMQ; 3ZV2; 4BJO; 4I8N; 4QAH; 4QBE
Drugs and Mode of Action
Drug(s) Hydrogen peroxide Drug Info Approved Infections [539576], [551871]
TRYPAN BLUE Drug Info Approved Colour dead tissues [531351]
ISIS 113715 Drug Info Phase 2 Type 2 diabetes [536259]
ISIS-PTP1Brx Drug Info Phase 2 Type 2 diabetes [524392]
ISIS-PTP1B Drug Info Preclinical Type 2 diabetes [551052]
ERTIPROTAFIB Drug Info Terminated Type 2 diabetes [527242]
Inhibitor 1,2,3,4,6-penta-O-galloyl-D-glucopyranose Drug Info [531140]
1,2,5-THIADIAZOLIDIN-3-ONE-1,1-DIOXIDE Drug Info [551374]
1,2-NAPHTHOQUINONE Drug Info [526377]
1-Iodyl-3-nitro-benzene Drug Info [525449]
1-Iodyl-4-nitro-benzene Drug Info [525449]
1-METHYL-3-PHENYL-1H-PYRAZOL-5-YLSULFAMIC ACID Drug Info [551391]
16-alphaH,17-isovaleryloxy-ent-kauran-19-oic acid Drug Info [528088]
18alpha-Glycyrrhetic acid Drug Info [528115]
18beta-Glycyrrhetic acid Drug Info [528115]
19alpha,24-dihydroxyurs-12-en-3-on-28-oic acid Drug Info [529697]
2-(Oxalyl-Amino)-Benzoic Acid Drug Info [551393]
2-Methyl-2,4-Pentanediol Drug Info [551393]
24-hydroxyursolic acid Drug Info [529697]
3,9-Dihydroxy-4-prenyl-[6aR,11aR]pterocarpan Drug Info [530454]
3-(4,5-Bis-biphenyl-4-yl-1H-imidazol-2-yl)-phenol Drug Info [526334]
3-(Oxalyl-Amino)-Naphthalene-2-Carboxylic Acid Drug Info [551393]
3-epi-masilinic acid Drug Info [530467]
3-Iodyl-benzoic acid Drug Info [525449]
3-isopropyl-4-(phenylthio)naphthalene-1,2-dione Drug Info [527986]
3-oxoolean-12-en-27-oic acid Drug Info [528115]
3alpha,24-dihydroxyolean-12-en-27-oic acid Drug Info [528115]
3beta,6beta-dihydroxyolean-12-en-27-oic acid Drug Info [528115]
3beta-acetoxyolean-12-en-27-oic acid Drug Info [528115]
3beta-hydroxyolean-12-en-27-oic acid Drug Info [528115]
3beta-hydroxyurs-12-en-27-oic acid Drug Info [528115]
4'-((2-butylbenzofuran-3-yl)methyl)biphenyl-4-ol Drug Info [530028]
4'-(2-butylbenzofuran-3-yl)biphenyl-4-ol Drug Info [530028]
4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione Drug Info [527986]
4-Iodyl-benzoic acid Drug Info [525449]
5-deoxyabyssinin II Drug Info [528828]
6-(Oxalyl-Amino)-1h-Indole-5-Carboxylic Acid Drug Info [551393]
Abyssinin I Drug Info [528828]
Abyssinin II Drug Info [528828]
Abyssinoflavanone VI Drug Info [528828]
Abyssinoflavanone VII Drug Info [528828]
Abyssinone-IV Drug Info [528537]
Abyssinone-VI-4-O-methyl ether Drug Info [528537]
Acetate Ion Drug Info [551393]
ALBAFURAN A Drug Info [530464]
Augustic acid Drug Info [530467]
B-Octylglucoside Drug Info [551393]
BURTTINONE Drug Info [529806]
CAULERPIN Drug Info [528096]
CHROMOTROPATE Drug Info [527017]
Compound 15 Drug Info [551393]
Compound 19 Drug Info [551393]
Compound 9 Drug Info [551393]
Cysteine Sulfenic Acid Drug Info [551391]
Cysteinesulfonic Acid Drug Info [551393]
Double Oxidized Cysteine Drug Info [551393]
DYSIDINE Drug Info [529869]
ERTIPROTAFIB Drug Info [529004]
ERYBREADIN B Drug Info [530454]
Erybreadin C Drug Info [530454]
Erybreadin D Drug Info [530454]
Erysubin E Drug Info [530454]
ERYTHRIBYSSIN A Drug Info [530454]
FOLITENOL Drug Info [530454]
FORMYLCHROMONE Drug Info [531033]
Hydrogen peroxide Drug Info [525449]
Iodyl-benzene Drug Info [525449]
Isochroman mono-carboxylic acid Drug Info [531033]
ISOTHIAZOLIDINONE ANALOG Drug Info [551374]
Isoxazolecarboxylic acid Drug Info [531033]
KR61639 Drug Info [535898]
Kuwanon J Drug Info [530464]
Kuwanon L Drug Info [527927]
Kuwanon R Drug Info [530464]
Kuwanon V Drug Info [530464]
LICOAGROCHACONE A Drug Info [530275]
LICOAGROCHALCONE A Drug Info [528828]
MASLINIC ACID Drug Info [530467]
Methyl 3beta-hydroxyolean-12-en-28-oate Drug Info [528115]
Methyl3beta-hydroxyolean-12-en-27-oate Drug Info [528115]
Mulberrofuran C Drug Info [527927]
Mulberrofuran D Drug Info [530464]
Mulberrofuran W Drug Info [530464]
NEORAUTENOL Drug Info [530454]
Novo Nordisk a/S Compound Drug Info [551393]
OHIOENSIN A Drug Info [529192]
Ohioensin C Drug Info [529192]
Ohioensin F Drug Info [529192]
Ohioensin G Drug Info [529192]
OLEANOLIC_ACID Drug Info [530332]
Oleanonic acid Drug Info [529697]
Oxalylaminobenzoic acid Drug Info [531033]
PARA-(BENZOYL)-PHENYLALANINE Drug Info [551374]
PHELLIGRIDIN I Drug Info [528656]
PNU177836 Drug Info [551393]
Pomolic acid Drug Info [529697]
RK-682 Drug Info [531115]
Rotungenic acid Drug Info [529697]
Sanggenon C Drug Info [527927]
Sanggenon G Drug Info [527927]
SIGMOIDIN A Drug Info [528828]
SIGMOIDIN B Drug Info [528828]
Sigmoidin F Drug Info [528828]
Sp7343-Sp7964 Drug Info [551393]
Spathodic acid Drug Info [529697]
TRYPAN BLUE Drug Info [527017]
URSOLIC ACID Drug Info [530454]
USIMINE A Drug Info [529326]
USNIC ACID Drug Info [529326]
UVAOL Drug Info [529697]
[[4-(Aminomethyl)Phenyl]Amino]Oxo-Acetic Acid, Drug Info [551393]
Modulator ISIS-PTP1Brx Drug Info [551949]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Adherens junction
Insulin signaling pathway
NetPath Pathway FSH Signaling Pathway
PANTHER Pathway Cadherin signaling pathway
Pathway Interaction Database Insulin Pathway
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
Signaling events mediated by PTP1B
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
Signaling events mediated by TCPTP
IGF1 pathway
EGF receptor (ErbB1) signaling pathway
Posttranslational regulation of adherens junction stability and dissassembly
PDGFR-beta signaling pathway
N-cadherin signaling events
Reactome Integrin alphaIIb beta3 signaling
Regulation of IFNG signaling
Regulation of IFNA signaling
Growth hormone receptor signaling
WikiPathways Insulin Signaling
Growth hormone receptor signaling
Leptin signaling pathway
Interferon gamma signaling
Interferon alpha/beta signaling
Integrin alphaIIb beta3 signaling
References
Ref 524392ClinicalTrials.gov (NCT01918865) Safety, Tolerability, and Efficacy of ISIS-PTP1BRx in Type 2 Diabetes. U.S. National Institutes of Health.
Ref 527242Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms. Mol Pharmacol. 2005 Jan;67(1):69-77. Epub 2004 Oct 8.
Ref 531351Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
Ref 536259Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone. Clin Pharmacokinet. 2006;45(8):789-801.
Ref 539576(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2448).
Ref 551052Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 525449Bioorg Med Chem Lett. 1999 Feb 8;9(3):353-6.Periodinates: a new class of protein tyrosine phosphatase inhibitors.
Ref 526334J Med Chem. 2002 May 23;45(11):2213-21.Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B.
Ref 526377Bioorg Med Chem Lett. 2002 Aug 5;12(15):1941-6.Synthesis and PTP1B inhibition of 1,2-naphthoquinone derivatives as potent anti-diabetic agents.
Ref 527017Bioorg Med Chem Lett. 2004 Apr 19;14(8):1923-6.Evans Blue and other dyes as protein tyrosine phosphatase inhibitors.
Ref 527927Bioorg Med Chem Lett. 2006 Mar 1;16(5):1426-9. Epub 2005 Dec 13.Protein tyrosine phosphatase 1B inhibitors from Morus root bark.
Ref 527986Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8. Epub 2006 Jan 24.Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.
Ref 528088Bioorg Med Chem Lett. 2006 Jun 1;16(11):3061-4. Epub 2006 Mar 20.Inhibition of protein tyrosine phosphatase 1B by diterpenoids isolated from Acanthopanax koreanum.
Ref 528096Bioorg Med Chem Lett. 2006 Jun 1;16(11):2947-50. Epub 2006 Mar 24.Two novel aromatic valerenane-type sesquiterpenes from the Chinese green alga Caulerpa taxifolia.
Ref 528115Bioorg Med Chem Lett. 2006 Jun 15;16(12):3273-6. Epub 2006 Mar 31.Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana.
Ref 528537J Nat Prod. 2006 Nov;69(11):1572-6.Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from Erythrina mildbraedii.
Ref 528656J Nat Prod. 2007 Feb;70(2):296-9. Epub 2007 Feb 6.Structures, biogenesis, and biological activities of pyrano[4,3-c]isochromen-4-one derivatives from the Fungus Phellinus igniarius.
Ref 528828J Nat Prod. 2007 Jun;70(6):1039-42. Epub 2007 May 10.Isoprenylated flavonoids from the stem bark of Erythrina abyssinica.
Ref 529004Bioorg Med Chem Lett. 2007 Oct 1;17(19):5357-60. Epub 2007 Aug 15.2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity.
Ref 529192Bioorg Med Chem Lett. 2008 Jan 15;18(2):772-5. Epub 2007 Nov 17.Ohioensins F and G: protein tyrosine phosphatase 1B inhibitory benzonaphthoxanthenones from the Antarctic moss Polytrichastrum alpinum.
Ref 529326J Nat Prod. 2008 Apr;71(4):710-2. Epub 2008 Feb 21.Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum.
Ref 529697J Nat Prod. 2008 Oct;71(10):1775-8. Epub 2008 Sep 18.Triterpenoids from the leaves of Diospyros kaki (persimmon) and their inhibitory effects on protein tyrosine phosphatase 1B.
Ref 529806Bioorg Med Chem. 2008 Dec 15;16(24):10356-62. Epub 2008 Oct 10.Flavanones from the stem bark of Erythrina abyssinica.
Ref 529869Bioorg Med Chem Lett. 2009 Jan 15;19(2):390-2. Epub 2008 Nov 24.A novel sesquiterpene quinone from Hainan sponge Dysidea villosa.
Ref 530028Bioorg Med Chem. 2009 Apr 1;17(7):2658-72. Epub 2009 Mar 5.Synthesis, activity and molecular modeling of a new series of chromones as low molecular weight protein tyrosine phosphatase inhibitors.
Ref 530275Bioorg Med Chem Lett. 2009 Sep 1;19(17):5155-7. Epub 2009 Jul 24.Inhibitory effect of chalcones and their derivatives from Glycyrrhiza inflata on protein tyrosine phosphatase 1B.
Ref 530332J Nat Prod. 2009 Sep;72(9):1620-6.Chemical Constituents of the Roots of Euphorbia micractina.
Ref 530454Bioorg Med Chem Lett. 2009 Dec 1;19(23):6745-9. Epub 2009 Oct 1.Cytotoxic and PTP1B inhibitory activities from Erythrina abyssinica.
Ref 530464Bioorg Med Chem Lett. 2009 Dec 1;19(23):6759-61. Epub 2009 Oct 7.Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis.
Ref 530467Bioorg Med Chem Lett. 2009 Dec 1;19(23):6618-22. Epub 2009 Oct 8.Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B.
Ref 531033Eur J Med Chem. 2010 Sep;45(9):3709-18. Epub 2010 May 15.Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents.
Ref 531115Bioorg Med Chem Lett. 2010 Sep 15;20(18):5398-401. Epub 2010 Aug 1.Prenylflavonoids from Glycyrrhiza uralensis and their protein tyrosine phosphatase-1B inhibitory activities.
Ref 531140J Nat Prod. 2010 Sep 24;73(9):1578-81.Bioactivity-guided isolation of 1,2,3,4,6-Penta-O-galloyl-D-glucopyranose from Paeonia lactiflora roots as a PTP1B inhibitor.
Ref 535898Discovery of a novel protein tyrosine phosphatase-1B inhibitor, KR61639: potential development as an antihyperglycemic agent. Eur J Pharmacol. 2004 Feb 6;485(1-3):333-9.
Ref 536259Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone. Clin Pharmacokinet. 2006;45(8):789-801.
Ref 549637US patent application no. 6,261,840, Antisense modulation of PTP1B expression.
Ref 551052Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
Ref 551054Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551391DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551949Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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