Target Information
| Target General Information | Top | |||||
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| Target ID |
T89529
(Former ID: TTDR01437)
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| Target Name |
PTPN1 messenger RNA (PTPN1 mRNA)
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| Synonyms |
Tyrosine-protein phosphatase non-receptor type 1 (mRNA); PTP-1B (mRNA)
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| Gene Name |
PTPN1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Ophthalmic devices/implants/grafts injury [ICD-11: PK97] | |||||
| 2 | Postoperative inflammation [ICD-11: 1A00-CA43] | |||||
| Function |
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. Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response.
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| BioChemical Class |
mRNA target
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| UniProt ID | ||||||
| EC Number |
EC 3.1.3.48
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| Sequence |
MEMEKEFEQIDKSGSWAAIYQDIRHEASDFPCRVAKLPKNKNRNRYRDVSPFDHSRIKLH
QEDNDYINASLIKMEEAQRSYILTQGPLPNTCGHFWEMVWEQKSRGVVMLNRVMEKGSLK CAQYWPQKEEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWP DFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKD PSSVDIKKVLLEMRKFRMGLIQTADQLRFSYLAVIEGAKFIMGDSSVQDQWKELSHEDLE PPPEHIPPPPRPPKRILEPHNGKCREFFPNHQWVKEETQEDKDCPIKEEKGSPLNAAPYG IESMSQDTEVRSRVVGGSLRGAQAASPAKGEPSLPEKDEDHALSYWKPFLVNMCVATVLT AGAYLCYRFLFNSNT Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
| 1 | Hydrogen peroxide | Drug Info | Approved | Infectious disease | [2], [3] | |
| 2 | TRYPAN BLUE | Drug Info | Approved | Ophthalmic surgery injury | [4] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | ISIS 113715 | Drug Info | Phase 2 | Type-2 diabetes | [5] | |
| 2 | ISIS-PTP1Brx | Drug Info | Phase 2 | Type-2 diabetes | [6] | |
| 3 | URSOLIC ACID | Drug Info | Phase 2 | Metabolic syndrome x | [7] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | ERTIPROTAFIB | Drug Info | Terminated | Type-2 diabetes | [8] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 89 Inhibitor drugs | + | ||||
| 1 | Hydrogen peroxide | Drug Info | [9] | |||
| 2 | TRYPAN BLUE | Drug Info | [1] | |||
| 3 | URSOLIC ACID | Drug Info | [12] | |||
| 4 | ERTIPROTAFIB | Drug Info | [13] | |||
| 5 | 1,2,3,4,6-penta-O-galloyl-D-glucopyranose | Drug Info | [14] | |||
| 6 | 1,2,5-THIADIAZOLIDIN-3-ONE-1,1-DIOXIDE | Drug Info | [15] | |||
| 7 | 1-Iodyl-3-nitro-benzene | Drug Info | [9] | |||
| 8 | 1-Iodyl-4-nitro-benzene | Drug Info | [9] | |||
| 9 | 1-METHYL-3-PHENYL-1H-PYRAZOL-5-YLSULFAMIC ACID | Drug Info | [16] | |||
| 10 | 16-alphaH,17-isovaleryloxy-ent-kauran-19-oic acid | Drug Info | [17] | |||
| 11 | 18alpha-Glycyrrhetic acid | Drug Info | [18] | |||
| 12 | 19alpha,24-dihydroxyurs-12-en-3-on-28-oic acid | Drug Info | [19] | |||
| 13 | 2-Methyl-2,4-Pentanediol | Drug Info | [20] | |||
| 14 | 24-hydroxyursolic acid | Drug Info | [19] | |||
| 15 | 3,9-Dihydroxy-4-prenyl-[6aR,11aR]pterocarpan | Drug Info | [12] | |||
| 16 | 3-(4,5-Bis-biphenyl-4-yl-1H-imidazol-2-yl)-phenol | Drug Info | [21] | |||
| 17 | 3-(Oxalyl-Amino)-Naphthalene-2-Carboxylic Acid | Drug Info | [20] | |||
| 18 | 3-epi-masilinic acid | Drug Info | [22] | |||
| 19 | 3-isopropyl-4-(phenylthio)naphthalene-1,2-dione | Drug Info | [23] | |||
| 20 | 3-oxoolean-12-en-27-oic acid | Drug Info | [18] | |||
| 21 | 3alpha,24-dihydroxyolean-12-en-27-oic acid | Drug Info | [18] | |||
| 22 | 3beta,6beta-dihydroxyolean-12-en-27-oic acid | Drug Info | [18] | |||
| 23 | 3beta-acetoxyolean-12-en-27-oic acid | Drug Info | [18] | |||
| 24 | 3beta-hydroxyolean-12-en-27-oic acid | Drug Info | [18] | |||
| 25 | 3beta-hydroxyurs-12-en-27-oic acid | Drug Info | [18] | |||
| 26 | 4'-((2-butylbenzofuran-3-yl)methyl)biphenyl-4-ol | Drug Info | [24] | |||
| 27 | 4'-(2-butylbenzofuran-3-yl)biphenyl-4-ol | Drug Info | [24] | |||
| 28 | 4-(p-toluidino)-3-isopropylnaphthalene-1,2-dione | Drug Info | [23] | |||
| 29 | 4-Iodyl-benzoic acid | Drug Info | [9] | |||
| 30 | 5-deoxyabyssinin II | Drug Info | [25] | |||
| 31 | 6-(Oxalyl-Amino)-1h-Indole-5-Carboxylic Acid | Drug Info | [20] | |||
| 32 | Abyssinin I | Drug Info | [25] | |||
| 33 | Abyssinin II | Drug Info | [25] | |||
| 34 | Abyssinoflavanone VI | Drug Info | [25] | |||
| 35 | Abyssinoflavanone VII | Drug Info | [25] | |||
| 36 | Abyssinone-IV | Drug Info | [26] | |||
| 37 | Abyssinone-VI-4-O-methyl ether | Drug Info | [26] | |||
| 38 | Acetate Ion | Drug Info | [20] | |||
| 39 | ALBAFURAN A | Drug Info | [27] | |||
| 40 | Augustic acid | Drug Info | [22] | |||
| 41 | B-Octylglucoside | Drug Info | [20] | |||
| 42 | BURTTINONE | Drug Info | [28] | |||
| 43 | CAULERPIN | Drug Info | [29] | |||
| 44 | CHROMOTROPATE | Drug Info | [1] | |||
| 45 | Cysteinesulfonic Acid | Drug Info | [20] | |||
| 46 | Double Oxidized Cysteine | Drug Info | [20] | |||
| 47 | Erybreadin C | Drug Info | [12] | |||
| 48 | Erybreadin D | Drug Info | [12] | |||
| 49 | Erysubin E | Drug Info | [12] | |||
| 50 | ERYTHRIBYSSIN A | Drug Info | [12] | |||
| 51 | FOLITENOL | Drug Info | [12] | |||
| 52 | FORMYLCHROMONE | Drug Info | [30] | |||
| 53 | Iodyl-benzene | Drug Info | [9] | |||
| 54 | Isochroman mono-carboxylic acid | Drug Info | [30] | |||
| 55 | ISOTHIAZOLIDINONE ANALOG | Drug Info | [15] | |||
| 56 | Isoxazolecarboxylic acid | Drug Info | [30] | |||
| 57 | KR61639 | Drug Info | [32] | |||
| 58 | Kuwanon J | Drug Info | [27] | |||
| 59 | Kuwanon L | Drug Info | [33] | |||
| 60 | Kuwanon R | Drug Info | [27] | |||
| 61 | Kuwanon V | Drug Info | [27] | |||
| 62 | LICOAGROCHACONE A | Drug Info | [34] | |||
| 63 | LICOAGROCHALCONE A | Drug Info | [25] | |||
| 64 | MASLINIC ACID | Drug Info | [22] | |||
| 65 | Methyl 3beta-hydroxyolean-12-en-28-oate | Drug Info | [18] | |||
| 66 | Methyl3beta-hydroxyolean-12-en-27-oate | Drug Info | [18] | |||
| 67 | Mulberrofuran D | Drug Info | [27] | |||
| 68 | Mulberrofuran W | Drug Info | [27] | |||
| 69 | NEORAUTENOL | Drug Info | [12] | |||
| 70 | OHIOENSIN A | Drug Info | [35] | |||
| 71 | Ohioensin F | Drug Info | [35] | |||
| 72 | OLEANOLIC_ACID | Drug Info | [36] | |||
| 73 | Oleanonic acid | Drug Info | [19] | |||
| 74 | Oxalylaminobenzoic acid | Drug Info | [30] | |||
| 75 | PARA-(BENZOYL)-PHENYLALANINE | Drug Info | [15] | |||
| 76 | PHELLIGRIDIN I | Drug Info | [37] | |||
| 77 | RK-682 | Drug Info | [38] | |||
| 78 | Rotungenic acid | Drug Info | [19] | |||
| 79 | Sanggenon C | Drug Info | [33] | |||
| 80 | Sanggenon G | Drug Info | [33] | |||
| 81 | SIGMOIDIN A | Drug Info | [25] | |||
| 82 | SIGMOIDIN B | Drug Info | [25] | |||
| 83 | Sigmoidin F | Drug Info | [25] | |||
| 84 | Sp7343-Sp7964 | Drug Info | [20] | |||
| 85 | Spathodic acid | Drug Info | [19] | |||
| 86 | USIMINE A | Drug Info | [39] | |||
| 87 | USNIC ACID | Drug Info | [39] | |||
| 88 | UVAOL | Drug Info | [19] | |||
| 89 | [[4-(Aminomethyl)Phenyl]Amino]Oxo-Acetic Acid, | Drug Info | [20] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | ISIS-PTP1Brx | Drug Info | [11] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Evans Blue and other dyes as protein tyrosine phosphatase inhibitors. Bioorg Med Chem Lett. 2004 Apr 19;14(8):1923-6. | |||||
| REF 2 | URL: 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 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5. | |||||
| REF 5 | Lack 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 6 | ClinicalTrials.gov (NCT01918865) Safety, Tolerability, and Efficacy of ISIS-PTP1BRx in Type 2 Diabetes. U.S. National Institutes of Health. | |||||
| REF 7 | ClinicalTrials.gov (NCT02337933) Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome. U.S. National Institutes of Health. | |||||
| REF 8 | Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms. Mol Pharmacol. 2005 Jan;67(1):69-77. | |||||
| REF 9 | Periodinates: a new class of protein tyrosine phosphatase inhibitors. Bioorg Med Chem Lett. 1999 Feb 8;9(3):353-6. | |||||
| REF 10 | Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009). | |||||
| REF 11 | Clinical pipeline report, company report or official report of ISIS Pharmaceuticals. | |||||
| REF 12 | Cytotoxic and PTP1B inhibitory activities from Erythrina abyssinica. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6745-9. | |||||
| REF 13 | 2-O-carboxymethylpyrogallol derivatives as PTP1B inhibitors with antihyperglycemic activity. Bioorg Med Chem Lett. 2007 Oct 1;17(19):5357-60. | |||||
| REF 14 | Bioactivity-guided isolation of 1,2,3,4,6-Penta-O-galloyl-D-glucopyranose from Paeonia lactiflora roots as a PTP1B inhibitor. J Nat Prod. 2010 Sep 24;73(9):1578-81. | |||||
| REF 15 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 16 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 17 | Inhibition of protein tyrosine phosphatase 1B by diterpenoids isolated from Acanthopanax koreanum. Bioorg Med Chem Lett. 2006 Jun 1;16(11):3061-4. | |||||
| REF 18 | Protein tyrosine phosphatase 1B inhibitory activity of triterpenes isolated from Astilbe koreana. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3273-6. | |||||
| REF 19 | Triterpenoids from the leaves of Diospyros kaki (persimmon) and their inhibitory effects on protein tyrosine phosphatase 1B. J Nat Prod. 2008 Oct;71(10):1775-8. | |||||
| REF 20 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 21 | Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B. J Med Chem. 2002 May 23;45(11):2213-21. | |||||
| REF 22 | Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6618-22. | |||||
| REF 23 | Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1905-8. | |||||
| REF 24 | Synthesis, activity and molecular modeling of a new series of chromones as low molecular weight protein tyrosine phosphatase inhibitors. Bioorg Med Chem. 2009 Apr 1;17(7):2658-72. | |||||
| REF 25 | Isoprenylated flavonoids from the stem bark of Erythrina abyssinica. J Nat Prod. 2007 Jun;70(6):1039-42. | |||||
| REF 26 | Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from Erythrina mildbraedii. J Nat Prod. 2006 Nov;69(11):1572-6. | |||||
| REF 27 | Protein tyrosine phosphatase 1B inhibitors isolated from Morus bombycis. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6759-61. | |||||
| REF 28 | Flavanones from the stem bark of Erythrina abyssinica. Bioorg Med Chem. 2008 Dec 15;16(24):10356-62. | |||||
| REF 29 | Two novel aromatic valerenane-type sesquiterpenes from the Chinese green alga Caulerpa taxifolia. Bioorg Med Chem Lett. 2006 Jun 1;16(11):2947-50. | |||||
| REF 30 | Synthesis and evaluation of some novel dibenzo[b,d]furan carboxylic acids as potential anti-diabetic agents. Eur J Med Chem. 2010 Sep;45(9):3709-18. | |||||
| REF 31 | US patent application no. 6,261,840, Antisense modulation of PTP1B expression. | |||||
| REF 32 | Discovery 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 33 | Protein tyrosine phosphatase 1B inhibitors from Morus root bark. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1426-9. | |||||
| REF 34 | Inhibitory effect of chalcones and their derivatives from Glycyrrhiza inflata on protein tyrosine phosphatase 1B. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5155-7. | |||||
| REF 35 | Ohioensins F and G: protein tyrosine phosphatase 1B inhibitory benzonaphthoxanthenones from the Antarctic moss Polytrichastrum alpinum. Bioorg Med Chem Lett. 2008 Jan 15;18(2):772-5. | |||||
| REF 36 | Chemical Constituents of the Roots of Euphorbia micractina. J Nat Prod. 2009 Sep;72(9):1620-6. | |||||
| REF 37 | Structures, biogenesis, and biological activities of pyrano[4,3-c]isochromen-4-one derivatives from the Fungus Phellinus igniarius. J Nat Prod. 2007 Feb;70(2):296-9. | |||||
| REF 38 | Prenylflavonoids from Glycyrrhiza uralensis and their protein tyrosine phosphatase-1B inhibitory activities. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5398-401. | |||||
| REF 39 | Usimines A-C, bioactive usnic acid derivatives from the Antarctic lichen Stereocaulon alpinum. J Nat Prod. 2008 Apr;71(4):710-2. | |||||
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