Recent discovery and development of protein tyrosine phosphatase inhibitors

Expert Opinion on Therapeutic Patents

Volumn 12, Issue 6, 2002, Pages 871-905

  Blaskovich, Mark A ^a   Kim, Hwa Ok ^a  

^a Molecumetics Ltd   (United States)

Author keywords

Cancer; CD45; cdc25; Hyperglycaemia; Insulin resistance; LAR; Obesity; Protein tyrosine phosphatase; Protein tyrosine phosphatase inhibitor; PTP1B; TCPTP; Type II diabetes; VHR

Indexed keywords

2 METHYL FERVENULONE; 3 HEXADECANOYL 5 HYDROXYMETHYLTETRONIC ACID; 4' (PHOSPHODIFLUOROMETHYL) PHENYLALANINE; BENZBROMARONE; BISPHOSPHONIC ACID DERIVATIVE; CARBOXYLIC ACID; COSCINOSULFATE; DNACIN; DYSIDIOLIDE; FLUORENE DERIVATIVE; IMATINIB; NATURAL PRODUCT; NORNUCIFERINE; PEPTIDE DERIVATIVE; PHENYLALANINE DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; PROTEIN TYROSINE PHOSPHATASE; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; PULCHELLALACTAM; QUINONE DERIVATIVE; RK 682; STEVASTELIN A; SULFIRCIN; SULFONIC ACID DERIVATIVE; TETRAZOLE DERIVATIVE; TETRONIC ACID DERIVATIVE; TRASTUZUMAB; TYROSINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANADYL SULFATE;

ANIMAL EXPERIMENT; ANIMAL MODEL; CANCER; CELL FUNCTION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIABETES MELLITUS; DRUG ABSORPTION; DRUG DESIGN; DRUG IDENTIFICATION; DRUG RESEARCH; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; HUMAN; MOUSE; NONHUMAN; OSTEOPOROSIS; PATENT; PROTEIN PHOSPHORYLATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION;

EID: 0036079343     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.12.6.871     Document Type: Review

References (202)

1. Form and function in protein dephosphorylation
2. From form to function: Signalling by protein tyrosine phosphatases
3. Protein tyrosine phosphatases: A diverse family of intracellular and transmembrane enzymes
4. Protein-tyrosine phosphatases
5. Protein tyrosine phosphatases in signal transduction
6. The coordinated action of protein tyrosine phosphatases and kinases in cell signalling
7. Protein tyrosine phosphatases take off
8. 'Zip codes' direct intracellular protein tyrosine phosphatases to the correct cellular 'address'
9. The phosphorylation of proteins on tyrosine: Its role in cell growth and disease
10. Protein-tyrosine phosphatases: Biological function, structural characteristics and mechanism of catalysis
11. Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signalling
12. Introduction: Protein phosphorylation and signalling
13. Structural basis for control by phosphorylation
14. Protein phosphatases-a phylogenetic perspective
15. Molecular reactions of protein phosphatases - Insights from structure and chemistry
16. Regulatory Mechanisms for receptor protein tyrosine phosphatases
17. Nonreceptor tyrosine phosphatases in cellular signalling: Regulation of mitogen-activated protein kinases
18. Antiphosphatases take the stage
19. Signalling - 2000 and beyond
20. Characterization of the major protein-tyrosine-phosphatases of human placenta
21. Purification of the major protein-tyrosine-phosphatases of human placenta
22. Combinatorial control of the specificity of protein tyrosine phosphatases
23. Initial sequencing and analysis of the human genome
24. The sequence of the human genome
25. Crystal structure of bovine heart phosphotyrosyl phosphatase at 2.2-Å resolution
26. Protein tyrosine phosphatases as adhesion receptors
27. The carbonic anhydrase domain of receptor tyrosine phosphatase is a functional ligand for the axonal cell recognition molecule contactin
28. Receptor protein tyrosine phosphatase PTPμ associates with cadherins and catenins in vivo
29. Association of human protein-tyrosine phosphatase κ with members of the armadillo family
30. Crystal structure of the tyrosine phosphatase SHP-2
31. Crystal structures of peptide complexes of the amino-terminal SH2 domain of the syp tyrosine phosphatase
32. Structural basis for phosphotyrosine peptide recognition by protein tyrosine phosphatase 1B
33. Identification of a second aryl phosphate-binding site in protein tyrosine phosphatase 1B: A paradigm for inhibitor design
34. cas as a substrate for the cytosolic protein tyrosine phosphatase ptp-pest
35. Combination of gene targeting and substrate trapping to identify substrates of protein tyrosine phosphatases using ptp-pest as a model
36. Structural basis for substrate specificity of protein-tyrosine phosphatase shp-1
37. Development of 'substrate-trapping' mutants to identify physiological substrates of protein tyrosine phosphatases
38. Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B
39. + channels in mice lacking protein tyrosine phosphatase ε
40. Visualization of intermediate and transition-state structures in protein-tyrosine phosphatase catalysis
41. Design and characterization of an improved protein tyrosine phosphatase substrate-trapping mutant
42. A pit stop at the ER
43. Imaging sites of receptor dephosphorylation by PTP1B on the surface of the enodplasmic reticulum
44. Association of set domain and myotubularin-related proteins modulates growth control
45. Protein tyrosine phosphatases: Mechanisms of catalysis and regulation
46. Form, function and regulation of protein tyrosine phosphatases and their involvement in human diseases
47. Dimerization-induced inhibition of receptor protein tyrosine phosphatase function through an inhibitory wedge
48. Structural basis for inhibition of receptor protein-tyrosine phosphatase-α by dimerization
49. Receptor-like protein tyrosine phosphatase α homodimerizes on the cell surface
50. Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-α
51. Leptin receptor activation of SH2 domain containing protein tyrosine phosphatase 2 modulates ob receptor signal transduction
52. Redox regulation of protein tyrosine phosphatases by hydrogen peroxide: Detecting sulfenic acid intermediates and examining reversible inactivation
53. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
54. Protein tyrosine phosphatases
55. Protein-tyrosine phosphatases: Structure, mechanism and inhibitor discovery
56. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1
57. Crystal structure of human protein tyrosine phosphatase 1B
58. Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by x-ray crystallography
59. Small molecule interactions with protein-tyrosine phosphatase PTP1B and their use in inhibitor design
60. Structural basis for inhibition of the protein tyrosine phosphatase 1B by phosphotyrosine peptide mimetics
61. Structure of protein tyrosine phosphatase 1B in complex with inhibitors bearing two phosphotyrosine mimetics
62. 2-(Oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases
63. Novel benzofuran and benzothiophene biophenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties
64. Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere inhibit protein tyrosine phosphatase 1B and augment insulin action
65. Synthesis and biological activity of a novel class of small molecular weight peptidomimetic competitive inhibitors of protein tyrosine phosphatase 1B
66. Investigation of potential bioisosteric replacements for the carboxy groups of peptidomimetic inhibitors of protein tyrosine phosphatase 1B: Identification of a tetrazole-containing inhibitor with cellular activity
67. Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases
68. Crystal structure of yersinia protein tyrosine phosphatase at 2.5å and the complex with tungstate
69. The X-ray crystal structures of yersinia tyrosine phosphatase with bound tungstate and nitrate
70. Crystal structure of the catalytic domain of protein-tyrosine phosphatase SHP-1
71. The crystal structure of domain 1 of receptor protein tyrosine phosphatase μ
72. Crystal structure of the tandem phosphatase domains of RPTP LAR
73. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A
74. 2/M phase transition of the cell cycle
75. Crystal structure of the dual specificity protein phosphatase VHR
76. Structural basis for the recognition of a bisphosphorylated MAPK peptide by human VHR protein phosphatase
77. The crystal structure of a low-molecular-weight phosphotyrosine protein phosphatase
78. Solution structure of a low molecular weight protein tyrosine phosphatase
79. Protein tyrosine phosphatases (PTPs) as drug targets: Inhibitors of PTP-1B for the treatment of diabetes
80. 129 of low molecular weight protein tyrosine phosphatase is involved in leaving group protonation
81. The catalytic role of aspartic acid-92 in a human dual-specific protein-tyrosine phosphatase
82. Kinetic and Mechanistic Characterization of a mammalian protein-tyrosine phosphatase, PTP1
83. Roles of aspartic acid-181 and serine-222 in intermediate formation and hydrolysis of the mammalian protein-tyrosine phosphatase PTP1
84. Transition-state structures for the native dual-specific phosphatase VHR and D92N and S131A mutants. contributions to the driving force for catalysis
85. Analysis of in vitro interactions of protein tyrosine phosphatase 1B with insulin receptors
86. Introduction: Phosphatases in the immune system
87. Protein tyrosine phosphatases: Prospects for therapeutics
88. Protein tyrosine phosphatases: Their role in insulin action and potential as drug targets
89. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B Gene
90. Increased energy expenditure, decreased adiposity and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice
91. Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-i-stimulated signalling
92. Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance
93. Modulation of insulin signal transduction by eutopic overexpression of the receptor-type protein-tyrosine phosphatase LAR
94. NMR analysis of regioselectivity in dephosphorylation of a triphosphotyrosyl dodecapeptide autophosphorylation site of the insulin receptor by a catalytic fragment of LAR phosphotyrosine phosphatase
95. Suppression of insulin receptor activation by overexpression of the protein-tyrosine phosphatase LAR in hepatoma cells
96. Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity
97. Deficient LAR expression decreases basal forebrain cholinergic neuronal size and hippocampal cholinergic innervation
98. Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit profound defects in glucose homeostasis
99. Protein-tyrosine phosphatase-1B acts as a negative regulator of insulin signal transduction
100. Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases
101. The CD45 tyrosine phosphatase: A positive and negative regulator of immune cell function
102. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease
103. Severe combined immunodeficiency with abnormalities in expression of the common leucocyte antigen, CD45
104. CD45-null transgenic mice reveal a positive regulatory role for CD45 in early thymocyte development, in the selection of CD4+CD8+ thymocytes and B cell maturation
105. Normal lymphocyte development but impaired cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice
106. Severe defects in immunity and hematopoiesis caused by SHP-1 protein-tyrosine-phosphatase deficiency
107. Protein-tyrosine phosphatase shp-2 regulates cell spreading, migration and focal adhesion
108. Regulation of early events in integrin signalling by protein tyrosine phosphatase SHP-2
109. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA Protein
110. Immune inhibitory receptors
111. Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: Regulators of B-cell signal transduction
112. Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling
113. Dual specificity phosphatases: A gene family for control of MAPK function
114. Protein phosphatases and the regulation of mitogen-activated protein kinase signalling
115. Extracellular signals and scores of phosphatases: All roads lead to map kinase
116. Cdc25 protein phosphatases in cell proliferation
117. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer
118. Lipid phosphatases in the immune system
119. Impaired learning with enhanced hippocampal long-term potentiation in PTPδ-deficient mice
120. Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor tyrosine phosphatase PTPσ
121. Neuroendocrine dysplasia in mice lacking protein tyrosine phosphatase σ
122. Protein tyrosine phosphatase εC selectively inhibits interleukin-6- and interleukin-10-induced JAK-STAT signalling
123. Protein-tyrosine phosphatase activity regulates osteoclast formation and function: Inhibition by alendronate
124. Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice
125. The T cell protein tyrosine phosphatase
126. 5Arg catalytic motif in phosphoester hydrolysis
127. Protein tyrosine kinases: Structure, substrate specificity and drug discovery
128. Phosphotyrosyl-protein phosphatase. Specific inhibition by Zn
129. Tyrosine phosphorylation in T cells is regulated by phosphatase activity: Studies with phenylarsine oxide
130. Thiophosphate derivatives as inhibitors of tyrosine phosphatases
131. Inhibition of protein tyrosine phosphatase by the antitumour agent gallium nitrate
132. Synthesis and characterization of a potent and selective protein tyrosine phosphatase inhibitor, 2-[(4-Methylthiopyridin-2-yl) methylsulfinyl]-benzimidazole
133. Inhibition of membrane phosphotyrosyl-protein phosphatase activity by vanadate
134. Phosphotyrosyl-protein phosphatase of TCRC-2 cells
135. Mechanism of inhibition of protein-tyrosine phosphatases by vanadate and pervanadate
136. Phosphoryltyrosyl mimetics in the design of peptide-based signal transduction inhibitors
137. 2Pmp
138. Potent and highly selective inhibitors of the protein tyrosine phosphatase 1B
139. Phosphonate inhibitors of protein-tyrosine and serine/threonine phosphatases
140. Synthesis of a difluorophosphonomethyl-containing phosphatase inhibitor designed from the X-ray structure of a PTP1B-bound ligand
141. Structure-based design and synthesis of small molecule protein-tyrosine phosphatase 1B inhibitors
142. Utilization of a peptide lead for the discovery of a novel PTP1B-binding motif
143. Novel phosphate mimetics for the design of nonpeptidyl inhibitors of protein tyrosine phosphatases
144. Synthesis and characterization of a novel class of protein tyrosine phosphatase inhibitors
145. Molecular modeling of protein tyrosine phosphatase 1B (PTP 1B) inhibitors
146. Novel hydroxyphosphonate inhibitors of CD-45 tyrosine phosphatase
147. Why is difluoromethyl phenylalanine a more potent inhibitory moiety than phosphonomethyl phenylalanine toward protein-tyrosine phosphatases?
148. Protein-tyrosine phosphatase inhibition by a peptide containing the phosphotyrosine mimetic, L-O-malonyltyrosine
149. Potent inhibition of protein-tyrosine phosphatase by phosphotyrosine-mimic containing cyclic peptides
150. 4′-O-[2-(2-Fluoromalonyl)]-L-Tyrosine: A Phosphotyrosyl Mimic for the Preparation of Signal Transduction Inhibitory Peptides
151. Potent inhibition of protein tyrosine phosphatase-1B using the phosphotyrosyl mimetic fluoro-O-malonyl tyrosine (FOMT)
152. Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides
153. Examination of novel nonphosphorus-containing phosphotyrosyl mimetics against protein-tyrosine phosphatase-1B and demonstration of differential affinities toward Grb2 SH2 domains
154. Substrate specificities of catalytic fragments of protein tyrosine phosphatases (HPTPβ, LAR and CD45) toward phosphotyrosyl peptide substrates and thiophosphosphotyrosylated peptides as inhibitors
155. Protein tyrosine phosphatase substrate specificity: Size and phosphotyrosine positioning requirements in peptide substrates
156. Mapping the subsite preferences of protein tyrosine phosphatase PTP-1B using combinatorial chemistry approaches
157. Radio frequency tag encoded combinatorial library method for the discovery of cinnamic acid inhibitors of the protein tyrosine phosphatase PTP1B
158. A synthetic trissulfotyrosyl dodecapeptide analogue of the insulin receptor 1146-kinase domain inhibits tyrosine dephosphorylation of the insulin receptor in situ
159. Inhibition of protein tyrosine phosphatases PTP1B and CD45 by sulfotyrosyl peptides
160. Potent low molecular weight substrates for protein-tyrosine phosphatase
161. Potent nonpeptidyl inhibitors of protein tyrosine phosphatase 1B
162. Synthesis and Intrinsic Activities of Peptidic PTP1B Inhibitors
163. [Difluoro(phosphono)methyl]phenylalanin ε-Containing Peptide Inhibitors of Protein Tyrosine Phosphatases
164. Dysidiolide: A novel protein phosphatase inhibitor from the caribbean sponge Dysidea ethria de Laubenfels
165. Novel CDC25A phosphatase inhibitors from pyrolysis of 3-α-azido-B-homo-6-oxo-4-cholesten-7-one on silica gel
166. Natural products are biologically validated starting points in structural space for compound library development: Solid-phase synthesis of dysidiolide-derived phosphatase inhibitors
167. Total synthesis and determination of the absolute configuration of coscinosulfate. A new selective inhibitor of Cdc25 protein phosphatase
168. Synthesis and phosphatase inhibitory activity of analogs of sulfircin
169. Isolation of a novel protein tyrosine phosphatase inhibitor, 2-methyl-fervenulone and its precursors from Streptomyces
170. RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1 phase
171. Asymmetric synthesis of RK-682 and its analogs and evaluation of their protein phosphatase inhibitory activities
172. Phosphatoquinones A and B, novel tyrosine phosphatase inhibitors produced by Streptomyces sp
173. Aporphine alkaloids, CD45 protein tyrosine phosphatase inhibitors, from Rollinia Ulei
174. Pulchellalactam: A CD45 protein tyrosine phosphatase inhibitor from the marine fungus Corollospora pulchella
175. DnacinA1 and dnacin B1 are antitumour antibiotics that inhibit cdc25B phosphatase activity
176. PTP1B inhibition and antihyperglycemic activity in the ob/ob mouse model of novel 11-arylbenzo[b]-naphtho[2,3d]furans and 11-arylbenzo[b]-naphtho[2,3d]fthiophenes
177. Synthesis and PTP1B inhibition of novel 4-aryl-1-oxa-9-thiacyclopenta[b]-fluorenes
178. New Azolidinediones as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties
179. A targeted library of small-molecule, tyrosine and dual-specificity phosphatase inhibitors derived from a rational core design and random side chain variation
180. Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and Cdc25B inhibition
181. Structure based discovery of small molecule inhibitors targeted to protein tyrosine phosphatase 1B
182. Structure-based design of a low molecular weight, nonphosphorus, nonpeptide and highly selective inhibitor of protein tyrosine phosphatase 1B
183. α-Ketocarboxylic acid-based inhibitors of protein tyrosine phosphatases
184. Studies on menadione as an inhibitor of the cdc25 phosphatase
185. Naphthoquinone analogs as inactivators of cdc25 phosphatase
186. Selective inactivation of protein tyrosine phosphatase PTP1B by sulfone analogue of naphthoquinone
187. Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity phophatase Cdc25
188. α-Haloacetophenone derivatives as photoreversible covalent inhibitors of protein tyrosine phosphatases
189. Quiescent affinity inactivators of protein tyrosine phosphatases
190. Total synthesis of dephostatin, a novel protein tyrosine phosphatase inhibitor K
191. Synthesis and bioassay of a protein tyrosine phosphatase inhibitor, dephostatin
192. Synthesis and protein tyrosine phosphatase inhibitory activity of dephostatin analogs
193. Structure-activity relationship and rational design of 3,4-dephostatin derivatives as protein tyrosine phosphatase inhibitors
194. Suicide inactivation of human prostatic acid phosphatase and a phosphotyrosine phosphatase
195. Mechanism-based inactivation of prostatic acid phosphatase
196. Potent reversible inhibitors of the protein tyrosine phosphatase CD45
197. New Cdc25B Tyrosine Phosphatase Inhibitors, Nocardiones A and B, produced by Nocardia sp. TP-A0248: Taxonomy, fermentation, isolation, structural elucidation and biological Studies
198. Thiophosphorylated substrate analogs are potent active site-directed inhibitors of protein-tyrosine phosphatases
199. Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by Streptomyces
200. Stevastelins, a novel group of immunosuppressants, inhibit dual-specificity protein phosphatases
201. Is the PTP-ase vanadate complex is a true transition state analogue?
202. Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B