Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus

Sisir       Nandi; Mridula       Saxena
doi:10.2174/1568026620999200904121432
Abstract

Background: There has been growing interest in the development of highly potent and selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find potent and selective PTP1B inhibitors, which is currently considered as one of the best validated biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked, causing type II diabetes.
Objective: Insulin receptor sensitization is performed by a signal transduction mechanism via a selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor, autophosphorylation of the intracellular part of the receptor takes place, turning it into an active kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation. PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors.
Methods: Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives, 2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols, phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease mechanisms.
Results: The reader will gain an overview of the structure and biological activity of recently developed PTPs inhibitors.
Conclusion: The co-crystallized ligands and the screened inhibitors could be used as a template for the further design of potent congeners.
Keywords: Type-II diabetes mellitus, Protein tyrosine phosphatase 1B enzymes, PTP1B inhibitors, TCPTP, Cellular functions, Cell migration.
« Previous Next »
Graphical Abstract

[1] 
Wang, W.Q.; Sun, J.P.; Zhang, Z.Y. An overview of the protein tyrosine phosphatase superfamily. Curr. Top. Med. Chem.,  2003, 3(7), 739-748.
[http://dx.doi.org/10.2174/1568026033452302] [PMID: 12678841] 
[2] 
Alonso, A.; Sasin, J.; Bottini, N.; Friedberg, I.; Friedberg, I.; Osterman, A.; Godzik, A.; Hunter, T.; Dixon, J.; Mustelin, T. Protein tyrosine phosphatases in the human genome. Cell,  2004, 117(6), 699-711.
[http://dx.doi.org/10.1016/j.cell.2004.05.018] [PMID: 15186772] 
[3] 
Neel, B.G.; Tonks, N.K. Protein tyrosine phosphatases in signal transduction. Curr. Opin. Cell Biol.,  1997, 9(2), 193-204.
[http://dx.doi.org/10.1016/S0955-0674(97)80063-4] [PMID: 9069265] 
[4] 
Denu, J.M.; Dixon, J.E. Protein tyrosine phosphatases: mechanisms of catalysis and regulation. Curr. Opin. Chem. Biol.,  1998, 2(5), 633-641.
[http://dx.doi.org/10.1016/S1367-5931(98)80095-1] [PMID: 9818190] 
[5] 
Tonks, N.K.; Neel, B.G. Combinatorial control of the specificity of protein tyrosine phosphatases. Curr. Opin. Cell Biol.,  2001, 13(2), 182-195.
[http://dx.doi.org/10.1016/S0955-0674(00)00196-4] [PMID: 11248552] 
[6] 
Schiller, K.R.; Mauro, L.J. Tyrosine phosphatases as regulators of skeletal development and metabolism. J. Cell. Biochem.,  2005, 96(2), 262-277.
[http://dx.doi.org/10.1002/jcb.20515] [PMID: 16052478] 
[7] 
Blume-Jensen, P.; Hunter, T. Oncogenic kinase signalling. Nature,  2001, 411(6835), 355-365.
[http://dx.doi.org/10.1038/35077225] [PMID: 11357143] 
[8] 
Montalibet, J.; Kennedy, B.P. Therapeutic strategies for targeting PTP1B in diabetes. Drug Discov. Today Ther. Strateg.,  2005, 2, 129-135.
[http://dx.doi.org/10.1016/j.ddstr.2005.05.002] 
[9] 
Cook, W.S.; Unger, R.H. Protein tyrosine phosphatase 1B: a potential leptin resistance factor of obesity. Dev. Cell,  2002, 2(4), 385-387.
[http://dx.doi.org/10.1016/S1534-5807(02)00158-2] [PMID: 11970889] 
[10] 
Shankar, A.; Agrawal, N.; Sharma, M.; Pandey, A.; Girdhar, K.; Pandey, M. Role of protein tyrosine phosphatases in plants. Curr. Genomics,  2015, 16(4), 224-236.
[http://dx.doi.org/10.2174/1389202916666150424234300] [PMID: 26962298] 
[11] 
Fauman, E.B.; Saper, M.A. Structure and function of the protein tyrosine phosphatases. Trends Biochem. Sci.,  1996, 21(11), 413-417.
[http://dx.doi.org/10.1016/S0968-0004(96)10059-1] [PMID: 8987394] 
[12] 
Zhang, Z.Y. Protein tyrosine phosphatases: prospects for therapeutics. Curr. Opin. Chem. Biol.,  2001, 5(4), 416-423.
[http://dx.doi.org/10.1016/S1367-5931(00)00223-4] [PMID: 11470605] 
[13] 
Ruggiero, M.; Pazzagli, C.; Rigacci, S.; Magnelli, L.; Raugei, G.; Berti, A.; Chiarugi, V.P.; Pierce, J.H.; Camici, G.; Ramponi, G. Negative growth control by a novel low M(r) phosphotyrosine protein phosphatase in normal and transformed cells. FEBS Lett.,  1993, 326(1-3), 294-298.
[http://dx.doi.org/10.1016/0014-5793(93)81811-D] [PMID: 8100784] 
[14] 
Chiarugi, P.; Cirri, P.; Marra, F.; Raugei, G.; Camici, G.; Manao, G.; Ramponi, G. LMW-PTP is a negative regulator of insulin-mediated mitotic and metabolic signalling. Biochem. Biophys. Res. Commun.,  1997, 238(2), 676-682.
[http://dx.doi.org/10.1006/bbrc.1997.7355] [PMID: 9299573] 
[15] 
Mauro, L.J.; Dixon, J.E. ‘Zip codes’ direct intracellular protein tyrosine phosphatases to the correct cellular ‘address’. Trends Biochem. Sci.,  1994, 19(4), 151-155.
[http://dx.doi.org/10.1016/0968-0004(94)90274-7] [PMID: 8016862] 
[16] 
Thareja, S.; Aggarwal, S.; Bhardwaj, T.R.; Kumar, M. Protein tyrosine phosphatase 1B inhibitors: a molecular level legitimate approach for the management of diabetes mellitus. Med. Res. Rev.,  2012, 32(3), 459-517.
[http://dx.doi.org/10.1002/med.20219] [PMID: 20814956] 
[17] 
Cheng, A.; Dubé, N.; Gu, F.; Tremblay, M.L. Coordinated action of protein tyrosine phosphatases in insulin signal transduction. Eur. J. Biochem.,  2002, 269(4), 1050-1059.
[http://dx.doi.org/10.1046/j.0014-2956.2002.02756.x] [PMID: 11856336] 
[18] 
Penninger, J.M.; Irie-Sasaki, J.; Sasaki, T.; Oliveira-dos-Santos, A.J. CD45: new jobs for an old acquaintance. Nat. Immunol.,  2001, 2(5), 389-396.
[http://dx.doi.org/10.1038/87687] [PMID: 11323691] 
[19] 
Qu, C.K. Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response. Biochim. Biophys. Acta,  2002, 1592(3), 297-301.
[http://dx.doi.org/10.1016/S0167-4889(02)00322-1] [PMID: 12421673] 
[20] 
Hoffman, B.T.; Nelson, M.R.; Burdick, K.; Baxter, S.M. Protein tyrosine phosphatases: strategies for distinguishing proteins in a family containing multiple drug targets and anti-targets. Curr. Pharm. Des.,  2004, 10(10), 1161-1181.
[http://dx.doi.org/10.2174/1381612043452659] [PMID: 15078147] 
[21] 
Tiganis, T.; Kemp, B.E.; Tonks, N.K. The protein-tyrosine phosphatase TCPTP regulates epidermal growth factor receptor-mediated and phosphatidylinositol 3-kinase-dependent signaling. J. Biol. Chem.,  1999, 274(39), 27768-27775.
[http://dx.doi.org/10.1074/jbc.274.39.27768] [PMID: 10488121] 
[22] 
You-Ten, K.E.; Muise, E.S.; Itié, A.; Michaliszyn, E.; Wagner, J.; Jothy, S.; Lapp, W.S.; Tremblay, M.L. Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice. J. Exp. Med.,  1997, 186(5), 683-693.
[http://dx.doi.org/10.1084/jem.186.5.683] [PMID: 9271584] 
[23] 
Galic, S.; Hauser, C.; Kahn, B.B.; Haj, F.G.; Neel, B.G.; Tonks, N.K.; Tiganis, T. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol. Cell. Biol.,  2005, 25(2), 819-829.
[http://dx.doi.org/10.1128/MCB.25.2.819-829.2005] [PMID: 15632081] 
[24] 
Lee, K.; Burke, T.R., Jr CD45 protein-tyrosine phosphatase inhibitor development. Curr. Top. Med. Chem.,  2003, 3(7), 797-807.
[http://dx.doi.org/10.2174/1568026033452267] [PMID: 12678845] 
[25] 
Zhang, Z.Y. Chemical and mechanistic approaches to the study of protein tyrosine phosphatases. Acc. Chem. Res.,  2003, 36(6), 385-392.
[http://dx.doi.org/10.1021/ar020122r] [PMID: 12809524] 
[26] 
Hooft van Huijsduijnen, R.; Sauer, W.H.B.; Bombrun, A.; Swinnen, D. Prospects for inhibitors of protein tyrosine phosphatase 1B as antidiabetic drugs. J. Med. Chem.,  2004, 47(17), 4142-4146.
[http://dx.doi.org/10.1021/jm030629n] [PMID: 15293983] 
[27] 
Dewang, P.M.; Hsu, N.M.; Peng, S.Z.; Li, W.R. Protein tyrosine phosphatases and their inhibitors. Curr. Med. Chem.,  2005, 12(1), 1-22.
[http://dx.doi.org/10.2174/0929867053363504] [PMID: 15638728] 
[28] 
Bialy, L.; Waldmann, H. Inhibitors of protein tyrosine phosphatases: next-generation drugs? Angew. Chem. Int. Ed. Engl.,  2005, 44(25), 3814-3839.
[http://dx.doi.org/10.1002/anie.200461517] [PMID: 15900534] 
[29] 
Burke, T.R., Jr; Zhang, Z.Y. Protein-tyrosine phosphatases: structure, mechanism, and inhibitor discovery. Biopolymers,  1998, 47(3), 225-241.
[http://dx.doi.org/10.1002/(SICI)1097-0282(1998)47:3<225:AID-BIP3>3.0.CO;2-O] [PMID: 9817026] 
[30] 
Liu, G.; Trevillyan, J.M. Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and type II diabetes. Curr. Opin. Investig. Drugs,  2002, 3(11), 1608-1616.
[PMID: 12476961] 
[31] 
Olichon-Berthe, C.; Hauguel-De Mouzon, S.; Péraldi, P.; Van Obberghen, E.; Le Marchand-Brustel, Y. Insulin receptor dephosphorylation by phosphotyrosine phosphatases obtained from insulin-resistant obese mice. Diabetologia,  1994, 37(1), 56-60.
[http://dx.doi.org/10.1007/BF00428778] [PMID: 8150231] 
[32] 
Taylor, S.D. Inhibitors of protein tyrosine phosphatase 1B (PTP1B). Curr. Top. Med. Chem.,  2003, 3(7), 759-782.
[http://dx.doi.org/10.2174/1568026033452311] [PMID: 12678843] 
[33] 
Kumar, S.; Liang, F.; Lawrence, D.S.; Zhang, Z.Y. Small molecule approach to studying protein tyrosine phosphatase. Methods,  2005, 35(1), 9-21.
[http://dx.doi.org/10.1016/j.ymeth.2004.07.003] [PMID: 15588981] 
[34] 
Tonks, N.K.; Diltz, C.D.; Fischer, E.H. Purification of the major protein-tyrosine-phosphatases of human placenta. J. Biol. Chem.,  1988, 263(14), 6722-6730.
[PMID: 2834386] 
[35] 
Barford, D.; Flint, A.J.; Tonks, N.K. Crystal structure of human protein tyrosine phosphatase 1B. Science,  1994, 263(5152), 1397-1404.
[http://dx.doi.org/10.1126/science.8128219] [PMID: 8128219] 
[36] 
Verma, M.; Gupta, S.J.; Chaudhary, A.; Garg, V.K. Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review. Bioorg. Chem.,  2017, 70, 267-283.
[http://dx.doi.org/10.1016/j.bioorg.2016.12.004] [PMID: 28043717] 
[37] 
Haque, A.; Andersen, J.N.; Salmeen, A.; Barford, D.; Tonks, N.K. Conformation-sensing antibodies stabilize the oxidized form of PTP1B and inhibit its phosphatase activity. Cell,  2011, 147(1), 185-198.
[38] 
Barford, D.; Jia, Z.; Tonks, N.K. Protein tyrosine phosphatases take off. Nat. Struct. Biol.,  1995, 2(12), 1043-1053.
[http://dx.doi.org/10.1038/nsb1295-1043] [PMID: 8846213] 
[39] 
Zhang, Z.Y.; Lee, S.Y. PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity. Expert Opin. Investig. Drugs,  2003, 12(2), 223-233.
[http://dx.doi.org/10.1517/13543784.12.2.223] [PMID: 12556216] 
[40] 
Lantz, K.A.; Hart, S.G.; Planey, S.L.; Roitman, M.F.; Ruiz-White, I.A.; Wolfe, H.R.; McLane, M.P. Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. Obesity (Silver Spring),  2010, 18(8), 1516-1523.
[http://dx.doi.org/10.1038/oby.2009.444] [PMID: 20075852] 
[41] 
Fukuda, S.; Ohta, T.; Sakata, S.; Morinaga, H.; Ito, M.; Nakagawa, Y.; Tanaka, M.; Matsushita, M. Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT-551. Diabetes Obes. Metab.,  2010, 12(4), 299-306.
[http://dx.doi.org/10.1111/j.1463-1326.2009.01162.x] [PMID: 20380650] 
[42] 
 Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. WO101569,  2004.
[43] 

                         Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. WO101568,
                     2004.
[44] 

                        Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. US0229890,
                     2004.
[45] 

                         Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. US0270445,
                     2007.
[46] 

                        Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. US7262297,
                     2007.
[47] 

                         Hoffmann-La Roche Inc. Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitor. US7226915,
                     2007.
[48] 

                        Hoffmann-La Roche Inc. Pyrimido[5,4-E][1,2,4]triazine-5,7- diamine compounds as protein tyrosine phosphatases inhibitors. US6642381, 
                     2003.
[49] 

                         Hoffmann-La Roche Inc. Pyrimido[5,4-E][1,2,4]triazine-5,7- diamine compounds as protein tyrosine phosphatases inhibitors. US0153756, 
                     2003.
[50] 
Pandey, G.; Saxena, A.K. 3D QSAR studies on protein tyrosine phosphatase 1B inhibitors: comparison of the quality and predictivity among 3D QSAR models obtained from different conformer-based alignments. J. Chem. Inf. Model.,  2006, 46(6), 2579-2590.
[http://dx.doi.org/10.1021/ci600224n] [PMID: 17125198] 
[51] 
Saxena, A.K.; Pandey, G.; Gupta, S.; Singh, A.B.; Srivastava, A.K. Synthesis of protein tyrosine phosphatase 1B inhibitors: model validation and docking studies. Bioorg. Med. Chem. Lett.,  2009, 19(8), 2320-2323.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.058] [PMID: 19282172] 
[52] 
Gupta, S.; Pandey, G.; Rahuja, N.; Srivastava, A.K.; Saxena, A.K. Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors. Bioorg. Med. Chem. Lett.,  2010, 20(19), 5732-5734.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.008] [PMID: 20797859] 
[53] 
Balaramnavar, V.M.; Srivastava, R.; Rahuja, N.; Gupta, S.; Rawat, A.K.; Varshney, S.; Chandasana, H.; Chhonker, Y.S.; Doharey, P.K.; Kumar, S.; Gautam, S.; Srivastava, S.P.; Bhatta, R.S.; Saxena, J.K.; Gaikwad, A.N.; Srivastava, A.K.; Saxena, A.K. Identification of novel PTP1B inhibitors by pharmacophore based virtual screening, scaffold hopping and docking. Eur. J. Med. Chem.,  2014, 87, 578-594.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.097] [PMID: 25299681] 
[54] 
Gupta, S.; Varshney, K.; Srivastava, R.; Rahuja, N.; Rawat, A.K.; Srivastava, A.K.; Saxena, A.K. Identification of novel urea derivatives as PTP1B inhibitors: Synthesis, biological evaluation and structure–activity relationships. MedChemComm,  2013, 4, 382-1387.
[http://dx.doi.org/10.1039/c3md00138e] 
[55] 
Varshney, K.; Gupta, S.; Rahuja, N.; Rawat, A.K.; Singh, N.; Tamarkar, A.K.; Srivastava, A.K.; Saxena, A.K. Synthesis, structure-activity relationship and docking studies of substituted aryl thiazolyl phenylsulfonamides as potential protein tyrosine phosphatase 1B inhibitors. ChemMedChem,  2012, 7(7), 1185-1190.
[http://dx.doi.org/10.1002/cmdc.201200197] [PMID: 22615198] 
[56] 
Scapin, G.; Patel, S.B.; Becker, J.W.; Wang, Q.; Desponts, C.; Waddleton, D.; Skorey, K.; Cromlish, W.; Bayly, C.; Therien, M.; Gauthier, J.Y.; Li, C.S.; Lau, C.K.; Ramachandran, C.; Kennedy, B.P.; Asante-Appiah, E. The structural basis for the selectivity of benzotriazole inhibitors of PTP1B. Biochemistry,  2003, 42(39), 11451-11459.
[http://dx.doi.org/10.1021/bi035098j] [PMID: 14516196] 
[57] 
Chandrasekharappa, A.P.; Badiger, S.E.; Dubey, P.K.; Panigrahi, S.K.; Manukonda, S.R. Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(9), 2579-2584.
[http://dx.doi.org/10.1016/j.bmcl.2013.02.109] [PMID: 23528300] 
[58] 
Chen, Y.T.; Tang, C.L.; Ma, W.P.; Gao, L.X.; Wei, Y.; Zhang, W.; Li, J.Y.; Li, J.; Nan, F.J. Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4-carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with improved cellular efficacy. Eur. J. Med. Chem.,  2013, 69, 399-412.
[http://dx.doi.org/10.1016/j.ejmech.2013.09.017] [PMID: 24090912] 
[59] 
Ye, D.; Zhang, Y.; Wang, F.; Zheng, M.; Zhang, X.; Luo, X.; Shen, X.; Jiang, H.; Liu, H. Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity. Bioorg. Med. Chem.,  2010, 18(5), 1773-1782.
[http://dx.doi.org/10.1016/j.bmc.2010.01.055] [PMID: 20153651] 
[60] 
Joshi, P.; Deora, G.S.; Rathore, V.; Tanwar, O.P.; Rawat, A.K.; Srivastava, A.K.; Jain, D. Synthesis, SAR and Docking Studies of Substituted Aryl phenylthiazolyl phenylcarboxamide as PTP-1B Inhibitors. Med. Chem. Res.,  2013, 22, 28-34.
[http://dx.doi.org/10.1007/s00044-012-0007-0] 
[61] 
Varshney, K.; Gupta, A.K.; Rawat, A.; Srivatava, R.; Mishra, A.; Saxena, M.; Srivastava, A.K.; Jain, S.; Saxena, A.K. Synthesis, SAR and docking studies of substituted aryl phenylthiazolyl phyenylcarboxamide as potential protein tyrosine phosphatase 1b (ptp1b) inhibitors. Chem. Biol. Drug Des.,  In Press
[62] 
Wang, W.L.; Huang, C.; Gao, L.X.; Tang, C.L.; Wang, J.Q.; Wu, M.C.; Sheng, L.; Chen, H.J.; Nan, F.J.; Li, J.Y.; Li, J.; Feng, B. Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B inhibitors. Bioorg. Med. Chem. Lett.,  2014, 24(8), 1889-1894.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.015] [PMID: 24684845] 
[63] 
Tang, Y.; Zhang, X.; Chen, Z.; Yin, W.; Nan, G.; Tian, J.; Ye, F.; Xiao, Z. Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy. Acta Pharm. Sin. B,  2018, 8(6), 919-932.
[http://dx.doi.org/10.1016/j.apsb.2018.05.001] [PMID: 30505661] 
[64] 
Joshi, P.; Deora, G.S.; Rathore, V.; Tanwar, O.; Rawat, A.K.; Srivastava, A.K.; Jain, D. Identification of ZINC02765569: a potent inhibitor of PTP1B by vHTS. Med. Chem. Res.,  2013, 22(1), 28-34.
[http://dx.doi.org/10.1007/s00044-012-0007-0] 
[65] 
Rakse, M.; Karthikeyan, C.; Deora, G.S.; Moorthy, N.S.; Rathore, V.; Rawat, A.K.; Srivastava, A.K.; Trivedi, P. Design, synthesis and molecular modelling studies of novel 3-acetamido-4-methyl benzoic acid derivatives as inhibitors of protein tyrosine phosphatase 1B. Eur. J. Med. Chem.,  2013, 70, 469-476.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.030] [PMID: 24185377] 
[66] 
Maheshwari, N.; Karthikeyan, C.; Bhadada, S.V.; Sahi, C.; Verma, A.K.; Hari Narayana Moorthy, N.S.; Trivedi, P. Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation. Bioorg. Chem.,  2018, 80, 145-150.
[http://dx.doi.org/10.1016/j.bioorg.2018.06.016] [PMID: 29925050] 
[67] 
Maheshwari, N.; Karthikeyan, C.; Bhadada, S.V.; Verma, A.K.; Sahi, C.; Moorthy, N.S.H.N.; Trivedi, P. Design, synthesis and biological evaluation of some tetrazole acetamide derivatives as novel non-carboxylic PTP1B inhibitors. Bioorg. Chem.,  2019, 92103221
[http://dx.doi.org/10.1016/j.bioorg.2019.103221] [PMID: 31499261] 
[68] 
Zhi, Y.; Gao, L.X.; Jin, Y.; Tang, C.L.; Li, J.Y.; Li, J.; Long, Y.Q. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem.,  2014, 22(14), 3670-3683.
[http://dx.doi.org/10.1016/j.bmc.2014.05.028] [PMID: 24906513] 
[69] 
Malamas, M.S.; Sredy, J.; Moxham, C.; Katz, A.; Xu, W.; McDevitt, R.; Adebayo, F.O.; Sawicki, D.R.; Seestaller, L.; Sullivan, D.; Taylor, J.R. Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties. J. Med. Chem.,  2000, 43(7), 1293-1310.
[http://dx.doi.org/10.1021/jm990560c] [PMID: 10753467] 
[70] 
Tang, Y.B.; Lu, D.; Chen, Z.; Hu, C.; Yang, Y.; Tian, J.Y.; Ye, F.; Wu, L.; Zhang, Z.Y.; Xiao, Z. Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(8), 2313-2318.
[http://dx.doi.org/10.1016/j.bmcl.2013.02.073] [PMID: 23499238] 
[71] 
Du, Y.; Ling, H.; Zhang, M.; Shen, J.; Li, Q. Discovery of novel, potent, selective and cellular active ADC type PTP1B inhibitors via fragment-docking-oriented de novel design. Bioorg. Med. Chem.,  2015, 23(15), 4891-4898.
[http://dx.doi.org/10.1016/j.bmc.2015.05.032] [PMID: 26100442] 
[72] 
Liu, P.; Du, Y.; Song, L.; Shen, J.; Li, Q. Novel, potent, selective and cellular active ABC type PTP1B inhibitors containing (methanesulfonyl-phenyl-amino)-acetic acid methyl ester phosphotyrosine mimetic. Bioorg. Med. Chem.,  2015, 23(21), 7079-7088.
[http://dx.doi.org/10.1016/j.bmc.2015.09.024] [PMID: 26481657] 
[73] 
Liu, P.; Du, Y.; Song, L.; Shen, J.; Li, Q. Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity. Eur. J. Med. Chem.,  2016, 118, 27-33.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.014] [PMID: 27123900] 
[74] 
Garg, A.; Sharma, A.; Krishnamoorthy, P.; Garg, J.; Virmani, D.; Sharma, T.; Stefanini, G.; Kostis, J.B.; Mukherjee, D.; Sikorskaya, E. Role of niacin in current clinical practice: a systematic review. Am. J. Med.,  2017, 130(2), 173-187.
[http://dx.doi.org/10.1016/j.amjmed.2016.07.038] [PMID: 27793642] 
[75] 
Reasner, C.A. Niaspan®: a powerful treatment option for ‘diabetic dyslipidaemia’. Eur. Heart J. Suppl.,  2005, 7, F48-F55.
[http://dx.doi.org/10.1093/eurheartj/sui043] 
[76] 
Cai, Z. 
                         Preparation of nicotinamide derivative as PTP1B inhibitor for the treatment of type 2 diabetes Patent CN 104725307A
                     2015.
[77] 
Cai, Z. 
                        Protein tyrosine phosphatase 1B (PTP1B) inhibitor containing nicotinamide structure, preparation method and application for treating type II diabetes Patent CN. 104725308A,
                     2015.
[78] 
Cai, Z. 
                         PTP1B inhibitor containing nicotinamide structure and application thereof for treating type 2 diabetes mellitus. Patent CN 104725309A,
                     2015.
[79] 
Cai, Z. 
                        Preparation of PTP1B inhibitors. Patent CN 104725311A,
                     2015.
[80] 
Cai, Z. 
                        Preparation of compound nicotinamide structure as PTP1B inhibitor for treating type 2 diabetes mellitus. Patent CN 104725312A
                     2015.
[81] 
Cai, Z. 
                         Preparation of compounds containing niacinamide and piperidine structure as the PTP1B inhibitor in the treatment of type 2 diabetes. Patent CN 104725353A
                     2015.
[82] 
Cai, Z. 
                        Preparation of compounds containing niacinamide and piperidine structure as PTP1B inhibitor for the treatment of type II diabetes. Patent CN 104725354A
                     2015.
[83] 
Cai, Z. 
                         PTP1B inhibitor containing niacinamide and piperidine structure and application thereof for treating type II diabetes mellitus. Patent CN 104725355A
                     2015.
[84] 
Cai, Z. 
                        PTP1B inhibitor containing nicotinamide structure and piperidine structure. Patent CN104788424A
                     2015.
[85] 
Cai, Z. 
                        Preparation of PTP1B inhibitor containing nicotinamide structure and piperidine structure and their application as antidiabetic agents. Patent CN 104788425A
                     2015.
[86] 
Ganou, C.A.; Eleftheriou, P.Th.; Theodosis-Nobelos, P.; Fesatidou, M.; Geronikaki, A.A.; Lialiaris, T.; Rekka, E.A. Docking analysis targeted to the whole enzyme: an application to the prediction of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives. SAR QSAR Environ. Res.,  2018, 29(2), 133-149.
[http://dx.doi.org/10.1080/1062936X.2017.1414874] [PMID: 29347844] 
[87] 
Cai, Z. 
                       Preparation of cyclopentadienyl compds. as PTP1B inhibitor for treating type 2 diabetes. Patent CN 104744396A,
                     2015.
[88] 
Cai, Z. 
                       Compound containing cyclopentadiene and cyanoaniline structure as PTP1B inhibitor for treating type 2 diabetes mellitus and its preparation. Patent CN 104744397A
                     2015.
[89] 
Cai, Z. 
                       Preparation of PTP1B inhibitor containing cyclopentadiene and aniline structure. Patent CN 104803937A
                     2015.
[90] 
Cai, Z. 
                         Preparation of cyclopentadiene compounds as PTP1B inhibitors for treating non-insulin-dependent diabetes. Patent CN 104803941A,
                     2015.
[91] 
Cai, Z. 
                        Aniline-thiazole-cyclopentadiene-acetamide as PTP1B inhibitor and their preparation. Patent CN 104803944A
                     2015.
[92] 
Cai, Z. 
                          Preparation of PTP1B inhibitor containing cyclopentadiene structure and their application as antidiabetic agents. Patent CN 104803942A, 
                     2015.
[93] 
Cai, Z. 
                        PTP1B inhibitor containing cyclopentadiene structure and thioaniline structure, and preparing method and application thereof. Patent CN 104803943A,
                     2015.
[94] 
Cai, Z. 
                       PTP1B inhibitor containing cyclopentadiene and aniline structure and application. Patent CN 104829552A
                     2015.
[95] 
Cai, Z. 
                       Preparation of halophenyl thiazole and cyclopentadiene compounds as PTP1B inhibitor for treating type 2 diabetes. Patent CN 104744398A,
                     2015.
[96] 
Cai, Z. 
                       PTP1B inhibitor containing cyclopentadiene structure and phenyl thiazole structure its preparation. Patent CN 104803938A
                     2015.
[97] 
Cai, Z. 
                          Preparation of cyclopentadiene and nitrophenylthiazole containing PTP1B inhibitors. Patent CN 104803939A
                     2015.
[98] 
Cai, Z. 
                         Preparation of N-[3-[(dimethylamino)phenyl]-2- thiazolyl][(dimethylamino)phenyl]methyl]cyclopentadiene-1- acetamide derivatives as PTP1B inhibitor useful for the treatment of type II diabetes Patent CN 104803940A,
                     2015.
[99] 
Cai, Z. 
                        PTP1B inhibitor containing cyclopentadiene structure and phenyl aniline structure, and application thereof. Patent CN 104803945A, 
                     2015.
[100] 
Meng, G.; Zheng, M.; Wang, M.; Tong, J.; Ge, W.; Zhang, J.; Zheng, A.; Li, J.; Gao, L.; Li, J. Design and synthesis of new potent PTP1B inhibitors with the skeleton of 2-substituted imino-3-substituted-5-heteroarylidene-1,3-thiazolidine-4-one: Part I. Eur. J. Med. Chem.,  2016, 122, 756-769.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.060] [PMID: 27526040] 
[101] 
Bhattarai, B.R.; Kafle, B.; Hwang, J.S.; Ham, S.W.; Lee, K.H.; Park, H.; Han, I.O.; Cho, H. Novel thiazolidinedione derivatives with anti-obesity effects: dual action as PTP1B inhibitors and PPAR-γ activators. Bioorg. Med. Chem. Lett.,  2010, 20(22), 6758-6763.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.130] [PMID: 20850970] 
[102] 
Bhattarai, B.R.; Kafle, B.; Hwang, J.S.; Khadka, D.; Lee, S.M.; Kang, J.S.; Ham, S.W.; Han, I.O.; Park, H.; Cho, H. Thiazolidinedione derivatives as PTP1B inhibitors with antihyperglycemic and antiobesity effects. Bioorg. Med. Chem. Lett.,  2009, 19(21), 6161-6165.
[http://dx.doi.org/10.1016/j.bmcl.2009.09.020] [PMID: 19783142] 
[103] 
Mahapatra, M.K.; Kumar, R.; Kumar, M. N-alkylated thiazolidine-2,4-dione analogs as PTP1B inhibitors: synthesis, biological activity, and docking studies. Med. Chem. Res.,  2017, 26, 1176-1183.
[http://dx.doi.org/10.1007/s00044-017-1823-z] 
[104] 
Qian, S.; Zhang, M.; He, Y.; Wang, W.; Liu, S. Recent advances in the development of protein tyrosine phosphatase 1B inhibitors for Type 2 diabetes. Future Med. Chem.,  2016, 8(11), 1239-1258.
[http://dx.doi.org/10.4155/fmc-2016-0064] [PMID: 27357615] 
[105] 
Maheshwari, N.; Karthikeyan, C.; Trivedi, P.; Moorthy, N.S.H.N. Recent advances in protein tyrosine phosphatase 1b targeted drug discovery for type ii diabetes and obesity. Curr. Drug Targets,  2018, 19(5), 551-575.
[http://dx.doi.org/10.2174/1389450118666170222143739] [PMID: 28228082] 
[106] 
Eleftheriou, P.; Geronikaki, A.; Petrou, A. PTP1b inhibition, a promising approach for the treatment of diabetes type ii. Curr. Top. Med. Chem.,  2019, 19(4), 246-263.
[http://dx.doi.org/10.2174/1568026619666190201152153] [PMID: 30714526] 
[107] 
Quang, T.H.; Ngan, N.T.; Yoon, C-S.; Cho, K-H.; Kang, D-G.; Lee, H-S.; Kim, Y.C.; Oh, H. Protein tyrosine phosphatase 1b inhibitors from the roots of cudrania tricuspidata. Molecules,  2015, 20(6), 11173-11183.
[http://dx.doi.org/10.3390/molecules200611173] [PMID: 26091075] 
[108] 
Kim, D.H.; Lee, S.; Chung, Y.W.; Kim, B.M.; Kim, H.; Kim, K.; Yang, K.M. Antiobesity and antidiabetes effects of a cudrania tricuspidata hydrophilic extract presenting ptp1b inhibitory potential. BioMed Res. Int.,  2016, 20168432759
[PMID: 26989693] 
[109] 
Yang, P.; Liu, D.Q.; Liang, T.J.; Li, J.; Zhang, H.Y.; Liu, A.H.; Guo, Y.W.; Mao, S.C. Bioactive constituents from the green alga Caulerpa racemosa. Bioorg. Med. Chem.,  2015, 23(1), 38-45.
[http://dx.doi.org/10.1016/j.bmc.2014.11.031] [PMID: 25497963] 
[110] 
Liu, L.; Zhang, J.; Chen, C.; Teng, J.; Wang, C.; Luo, D. Structure and biosynthesis of fumosorinone, a new protein tyrosine phosphatase 1B inhibitor firstly isolated from the entomogenous fungus Isaria fumosorosea. Fungal Genet. Biol.,  2015, 81, 191-200.
[http://dx.doi.org/10.1016/j.fgb.2015.03.009] [PMID: 25857260] 
[111] 
Nguyen, P.H.; Ji, D.J.; Han, Y.R.; Choi, J.S.; Rhyu, D.Y.; Min, B.S.; Woo, M.H. Selaginellin and biflavonoids as protein tyrosine phosphatase 1B inhibitors from Selaginella tamariscina and their glucose uptake stimulatory effects. Bioorg. Med. Chem.,  2015, 23(13), 3730-3737.
[http://dx.doi.org/10.1016/j.bmc.2015.04.007] [PMID: 25907369] 
[112] 
Onoda, T.; Li, W.; Sasaki, T.; Miyake, M.; Higai, K.; Koike, K. Identification and evaluation of magnolol and chrysophanol as the principle protein tyrosine phosphatase-1B inhibitory compounds in a Kampo medicine. Masiningan. J. Ethnopharmacol.,  2016, 186, 84-90.
[http://dx.doi.org/10.1016/j.jep.2016.03.063] [PMID: 27049294] 
[113] 
Wang, Y.; Yuk, H.J.; Kim, J.Y.; Kim, D.W.; Song, Y.H.; Tan, X.F.; Curtis-Long, M.J.; Park, K.H. Novel chromenedione derivatives displaying inhibition of protein tyrosine phosphatase 1B (PTP1B) from Flemingia philippinensis. Bioorg. Med. Chem. Lett.,  2016, 26(2), 318-321.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.021] [PMID: 26704263] 
[114] 
Yang, Y.; Tian, J.Y.; Ye, F.; Xiao, Z. Identification of natural products as selective PTP1B inhibitors via virtual screening. Bioorg. Chem.,  2020, 98103706
[http://dx.doi.org/10.1016/j.bioorg.2020.103706] [PMID: 32199302] 
Rights & Permissions Print Cite
Article Metrics
36
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1568026620999200904121432	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract
