PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity

Expert Opinion on Investigational Drugs

Volumn 12, Issue 2, 2003, Pages 223-233

  Zhang, Zhong Yin ^a   Lee, Seung Yub ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Insulin reisistance; Insulin signalling; Leptin resistance; Leptin signalling; Obesity; PTP1B; PTP1B inhibitors; Type 2 diabetes; Tyrosine phosphorylation

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; ENZYME ANTIBODY; ERTIPROTAFIB; GLUCOSE; INSULIN; INSULIN RECEPTOR; ISIS 113715; LEPTIN; LEPTIN RECEPTOR; LIPID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PTP 112; REGULATOR PROTEIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VANADIC ACID; VANADIC ACID DERIVATIVE;

CHEMICAL MODIFICATION; CLINICAL TRIAL; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; FEASIBILITY STUDY; HORMONE ACTION; HORMONE RESISTANCE; HUMAN; IN VIVO STUDY; INSULIN RESISTANCE; MOLECULAR SIZE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHYSICAL CHEMISTRY; PROTEIN ANALYSIS; PROTEIN PHOSPHORYLATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION;

ANIMALS; DIABETES MELLITUS; DIABETES MELLITUS, TYPE 2; ENZYME INHIBITORS; HUMANS; OBESITY; PROTEIN-TYROSINE-PHOSPHATASE; SIGNAL TRANSDUCTION;

EID: 0037317489     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.12.2.223     Document Type: Review

References (84)

1. HUNTER T: Signaling-2000 and beyond. Cell (2000) 100:113-127.
2. NEEL BG, TONKS NK: Protein tyrosine phosphatases in signal transduction. Curr. Opin. Cell Biol. (1997) 9:193-204.
3. LI L, DIXON JE: Form, function, and regulation of protein tyrosine phosphatases and their involvement in human diseases. Semin. Immunol. (2000) 12:75-84.
4. ZHANG ZY: Protein tyrosine phosphatases: prospects for therapeutics. Curr. Opin. Chem. Biol. (2001) 5:416-423.
5. COHEN P: Protein kinase - the major drug targets of the twenty-first century? Nature Rev. Drug Discov. (1999) 1:309-315.
6. MOLLER NPH, IVERSEN LF, ANDERSEN HS, MCCORMACK JG: Protein tyrosine phosphatases (PTPs) as drug targets: Inhibitors of PTP1B for the treatment of diabetes. Curr. Opin. Drug Discov. Dev. (2000) 3:527-540.
7. TAYLOR SI: Deconstructing Type 2 diabetes. Cell (1999) 97:9-12.
8. SPIEGELMAN BM, FLIER JS: Obesity and the regulation of energy balance. Cell (2001) 104:531-543.
9. KOPELMAN PG: Obesity as a medical problem. Nature (2000) 404:635-643.
10. AVRUCH J: Insulin signal transduction through protein kinase cascades. Mol. Cell. Biochem. (1998) 182:31-48.
11. SALTIEL AR, PESSIN JE: Insulin signaling pathways in time and space. Trends Cell Biol. (2002) 12:65-71.
12. KAHN CR. Insulin action, diabetogenes, and the cause of Type II diabetes. Diabetes (1994) 43:1066-1084.
13. CZECH MP, CORVERA S: Signaling mechanisms that regulate glucose transport. J. Biol. Chem. (1999) 274:1865-1868.
14. WHITE MF: The IRS-signalling system: a network of docking proteins that mediate insulin action. Mol. Cell. Biochem. (1998) 182:3-11.
15. RUDERMAN NB, KAPELLER R, WHITE MF, CANTLEY LC: Activation of phosphatidylinositol 3-kinase by insulin. Proc. Natl. Acad. Sci. USA (1990) 87:1411-1415.
16. CHEATHAM B, VLAHOS CJ, CHEATHAM L, WANG L, BLENIS J, KAHN CR: Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol. Cell. Biol. (1994) 14:4902-4911.
17. DOWNWARD J: Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. (1998) 10:262-267.
18. FRAME S, COHEN P: GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. (2001) 359:1-16.
19. REAVEN GM: Role of insulin resistance in human disease. Diabetes (1988) 37:1595-1607.
20. KRUSZYNSKA YT, OLEFSKY JM: Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus. J. Invest. Med. (1996) 44:413-428.
21. MORINVILLE A, MAYSINGER D, SHAVER A: From Vanadis to Attopos. vanadium compounds as pharmacological tools in cell death signaling. Trends Pharmacol. Sci. (1998) 19:452-460.
22. SEKAR N, LI J, SHECHTER Y: Vanadium salts as insulin substitutes: mechanism of action, a scientific and therapeutic tool in diabetes mellitus research. Crit. Rev. Biochem. Mol. Biol. (1996) 31:339-359.
23. EVANS JL, JALLAL B: Protein tyrosine phosphatases: their roles in insulin action and potential as drug targets. Expert Opin. Investig. Drugs (1999) 8:139-160.
24. FRANGIONI JV, BEAHM PH, SHIFRIN V, JOST CA, NEEL BG: The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence. Cell (1992) 68:545-560.
25. GOLDSTEIN BJ: Regulation of insulin receptor signaling by protein-tyrosine dephosphorylation. Receptor (1993) 3:1-15.
26. BYON JCH, KUSARI AB, KUSARI J: Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction. Mol. Cell. Biochem. (1998) 182:101-198.
27. KENNER KA, ANYANWU E, OLEFSKY JM, KUSARI J: Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling. J. Biol. Chem. (1996) 271:19810-19816.
28. SEELY BL, STAUBS PA, REICHART DR et al.: Protein tyrosine phosphatase 1B interacts with the activated insulin receptor. Diabetes (1996) 45:1379-1385.
29. BANDYOPADHYAY D, KUSARI A, KENNER KA et al.: Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin. J. Biol. Chem. (1997) 272:1639-1645.
30. WÄLCHLI S, CURCHOD M-L, PESCINI GOBERT R, ARKINSTALL S, HOOFT VAN HUIJSDUIJNEN R: Identification of tyrosine phosphatases that dephosphorylate the insulin receptor: a brute-force approach based on 'substrate-trapping' mutants. J. Biol. Chem. (2000) 275:9792-9796.
31. GOLDSTEIN BJ, BITTNER-KOWALCZYK A, WHITE MF, HARBECK M: Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. J. Biol. Chem. (2000) 275:4283-4289.
32. CALERA MR, VALLEGA G, PILCH PF: Dynamics of protein-tyrosine phosphatases in rat adipocytes. J. Biol. Chem. (2000) 275:6308-6312.
33. MCGUIRE MC, FIELDS RM, NYOMBA BL et al.: Abnormal regulation of protein tyrosine phosphatase activities in skeletal muscle of insulin-resistant humans. Diabetes (1991) 40:939-942.
34. KUSARI J, KENNER KA, SUH KI, HILL DE, HENRY RR: Skeletal muscle protein tyrosine phosphatase activity and tyrosine phosphatase 1B protein content are associated with insulin action and resistance. J. Clin. Invest. (1994) 93:1156-1162.
35. AHMAD F, GOLDSTEIN BJ: Increased abundance of specific skeletal muscle protein-tyrosine phosphatases in a genetic model of insulin-resistant obesity and diabetes mellitus. Metabolism (1995) 44:1175-1184.
36. KENNER KA, HILL DE, OLEFSKY JM et al.: Regulation of protein tyrosine phosphatases by insulin and insulin-like growth Factor I. J. Biol. Chem. (1993) 268:25455-25462.
37. MAEGAWA H, IDE R, HASEGAWA M et al.: Thiozolidine derivatives ameliorate high glucose-induced insulin resistance via the normalization of protein-tyrosine phosphatase activities. J. Biol. Chem. (1995) 270:7724-7730.
38. ELCHEBLY M, PAYETTE P, MICHALISZYN E et al.: Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science (1999) 283:1544-1548.
39. KLAMAN LD, BOSS O, PERONI OD et al.: Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice. Mol. Cell Biol. (2000) 20:5479-5489.
40. DEFRONZO R: Pharmacological therapy for Type 2 diabetes. Ann. Intern. Med. (1999) 17:281-303.
41. FORSELL PA, BOIE Y, MONTALIBET J, COLLINS S, KENNEDY BP: Genomic characterization of the human and mouse protein tyrosine phosphatase-1B genes. Gene (2000) 260:145-153.
42. LEMBERTAS AV, PERUSSE L, CHAGNON YC et al.: Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J. Clin. Invest. (1997) 100:1240-1247.
43. GHOSH S, WATANABE RM, VALLE TT et al.: The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to Type 2 diabetes. Am. J. Hum. Genet. (2000) 67:1174-1185.
44. ECHWALD SM, BACH H, VESTERGAARD H et al.: A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with Type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro. Diabetes (2002) 51:1-6.
45. MOK A, CAO H, ZINMAN B et al.: A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is associated with protection from diabetes or impaired glucose tolerance in Oji-Cree. J. Clin. Endocrinol. Metab. (2002) 87:724-727.
46. DI PAOLA R, FRITTITTA L, MISCIO G et al.: A variation in 3UTR of hPTP1B increases specific gene expression and associates with insulin resistance. Am. J. Hum. Genet. (2002) 70:806-812.
47. FRIEDMAN JM: Obesity in the new millennium. Nature (2000) 404:632-634.
48. TARTAGLIA LA, DEMBSKI M, WENG X et al.: Identification and expression cloning of a leptin receptor, OB-R. Cell (1995) 83:1263-1271.
49. AHIMA RS, PRABAKARAN D, MANTZOROS C: Role of leptin in the neuroendocrine response to fasting. Nature (1996) 382:250-252.
50. UNGER RH: Lipotoxic diseases. Ann. Rev. Med. (2002) 53:319-336.
51. SHIMABUKURO M, HIGA M, ZHOU YT, WANG MY, NEWGARD CB, UNGER RH: Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J. Biol. Chem. (1998) 273:32487-32490.
52. BJORBAEK C, UOTANI S, DA SILVA B, FLIER JS: Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem. (1997) 272:32686-32695.
53. COOK WS, UNGER RH: Protein tyrosine phosphatase 1B: a potential leptin resistance factor of obesity. Dev. Cell (2002) 2:385-387.
54. LI C, FRIEDMAN JM: Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates Ob receptor signaling transduction. Proc. Natl. Acad. Sci. USA (1999) 96:9677-9682.
55. CARPENTER LR, FARRUGGELLA TJ, SYMES A, KAROW ML, YANCOPOULOS GD, STAHL N: Enhancing leptin response by preventing SH2-containing phosphatase 2 interaction with Ob receptor. Proc. Natl. Acad. Sci. USA (1998) 95:6061-6066.
56. ZABOLOTNY JM, BENCE-HANULEC KK, STRICKER-KRONGRAD A et al.: PTP1B regulates leptin signal transduction in vivo. Dev. Cell (2002) 2:489-495.
57. CHENG A, UETANI N, SIMONCIC PD et al.: Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. Dev. Cell (2002) 2:497-503.
58. MYERS MP, ANDERSEN JN, CHENG A et al.: TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. J. Biol. Chem. (2001) 276:47771-47774.
59. AHMAD F, LI PM, MEYEROVITCH J, GOLDSTEIN BJ: Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway. J. Biol. Chem. (1995) 270:20503-20508.
60. KOLE HK, GARANT MJ, KOLE S, BERNIER M: A peptide-based protein-tyrosine phosphatase inhibitor specifically enhances insulin receptor function in intact cells. J. Biol. Chem. (1996) 271:14302-14307.
61. CHEN H, CONG LN, LI Y et al.: A phosphotyrosyl mimetic peptide reverses impairment of insulin-stimulated translocation of GLUT4 caused by overexpression of PTP1B in rat adipose cells. Biochemistry (1999) 38:384-389.
62. WROBEL J, SREDY J, MOXHAM C et al.: PTP1B inhibition and antihyperglycemic activity of novel 11-arylbenzo[b]naphtho[2,3-d]furans and 11-Arylbenzo[b]naphtho[2,3-d]thiophenes. J. Med. Chem. (1999) 42:3199-3202.
63. MALAMAS MS, SREDY J, MOXHAM C et al.: Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties. J. Med. Chem. (2000) 43:1293-1310.
64. TOBIN JF, TAM S: Recent advances in the development of small molecule inhibitors of PTP1B for the treatment of insulin resistance and Type II diabetes. Curr. Opin. Drug Discov. Devel. (2002) 5:500-512.
65. ZINKER BA, RONDINONE CM, TREVILLYAN JM: PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc. Natl. Acad. Sci. USA (2002) 99:11357-11362.
66. RONDINONE CM, TREVILLYAN JM, CLAMPIT J: Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes (2002) 51:2405-2411.
67. BURKE TR Jr, ZHANG ZY: Protein tyrosine phosphatases: structure, mechanism and inhibitor discovery. Biopolymers (Peptide Science) (1998) 47:225-241.
68. ZHANG ZY. Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development. Ann. Rev. Pharmacol. Toxicol. (2002) 42:209-234.
69. BLASKOVICH MA, KIM HO: Recent discovery and development of protein tyrosine phosphatase inhibitors. Expert Opin. Ther. Targets (2002) 12:871-905.
70. ZHANG ZY: Protein-tyrosine phosphatases: biological function, structural characteristics, and mechanism of catalysis. Crit. Rev. Biochem. Mol. Biol. (1998) 33:1-52.
71. BARFORD D: Structural studies of reversible protein phosphorylation and protein phosphatases. Biochem. Soc. Trans. (1999) 27:751-766.
72. PUIUS YA, ZHAO Y, SULLIVAN M, LAWRENCE DS, ALMO SC, ZHANG ZY. Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: A paradigm for inhibitor design. Proc. Natl. Acad. Sci. USA (1997) 94:13420-13425.
73. ZHANG ZY, MACLEAN D, THIEME-SEFLER AM et al.: Substrate specificity of the protein tyrosine phosphatases. Proc. Natl. Acad. Sci. USA (1993) 90:4446-4450.
74. JIA Z, BARFORD D, FLINT AJ,TONKS NK: Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B. Science (1995) 268:1754-1758.
75. VETTER SW, KENG YF, LAWRENCE DS, ZHANG ZY: Assessment of protein tyrosine phosphatse 1B substrate specificity using 'inverse alanine scanning'. J. Biol. Chem. (2000) 275:2265-2268.
76. SARMIENTO M, PUIUS YA. VETTER SW et al.: Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition. Biochemistry (2000) 39:8171-8179.
77. VETTER SW, ZHANG ZY: Probing the phosphopeptide specificities of protein tyrosine phosphatases, SH2 and PTB domains with combinatorial library methods. Curr. Prot. Pept. Sci. (2002) 3:365-397.
78. BLEASDALE JE, OGG D, PALAZUK BJ et al.: Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere inhibit protein tyrosine phosphatase 1B and augment insulin action. Biochemistry (2001) 40:5642-5654.
79. LILJEBRIS C, LARSEN SD, OGG D, PALAZUK BJ, BLEASDALE JE: Investigation of potential bioisosteric replacements for the carboxyl groups of peptidomimetic inhibitors of protein tyrosine phosphatase 1B: identification of a tetrazole-containing inhibitor with cellular activity. J. Med. Chem. (2002) 45:1785-1798.
80. IVERSEN LF, ANDERSEN HS, BRANNER S et al.: Structure-based design of a low molecular weight, nonphosphorus, nonpeptide, and highly selective inhibitor of protein-tyrosine phosphatase 1B. J. Biol. Chem. (2000) 275:10300-10307.
81. IVERSEN LF, ANDERSEN HS, MOLLER KB et al.: Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases. Biochemistry (2001) 40:14812-14820.
82. LIU G, TREVILLYAN JM: Protein tyrosine phosphatase 1B as a target for the treatment of impaired glucose tolerance and Type 2 diabetes. Curr. Opin. Investig. Drugs (2002) 3:1608-1616.
83. SHEN K, KENG YF, WU L, GUO XL, LAWRENCE DS, ZHANG ZY: Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial library and screening procedure. J. Biol. Chem. (2001) 276:47311-47319.
84. GUO XL, SHEN K, WANG F, LAWRENCE DS, ZHANG ZY. Probing the molecular basis for potent and selective PTP1B inhibition. J. Biol. Chem. (2002) 277:41014-41022.