Selective protein tyrosine phosphatase 1B inhibitors: Targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands

Journal of Medicinal Chemistry

Volumn 46, Issue 16, 2003, Pages 3437-3440

  Liu, Gang ^a,b   Xin, Zhili ^a   Liang, Heng ^a   Abad Zapatero, Cele ^a   Hajduk, Philip J ^a   Janowick, David A ^a,c   Szczepankiewicz, Bruce G ^a   Pei, Zhonghua ^a   Hutchins, Charles W ^a   Ballaron, Stephen J ^a   Stashko, Michael A ^a   Lubben, Thomas H ^a   Berg, Cathy E ^a   Rondinone, Cristina M ^a   Trevillyan, James M ^a   Jirousek, Michael R ^a,c  

^a ABBOTT LABORATORIES   (United States)

^b R4MC ^*  (United States)

^c PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOBENZOIC ACID; INSULIN; LEPTIN; PROTEIN TYROSINE PHOSPHATASE 1B INHIBITOR; PROTEIN TYROSINE PHOSPHATASE INHIBITOR; SALICYLIC ACID; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING SITE; CALORIMETRY; CELL MEMBRANE PERMEABILITY; CHEMICAL MODIFICATION; CHEMICAL REACTION; CONTROLLED STUDY; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENTROPY; ENZYME INHIBITION; ENZYME MECHANISM; GENE DISRUPTION; HUMAN; HUMAN CELL; LIGAND BINDING; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PHENOTYPE; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

CATALYTIC DOMAIN; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; PHOSPHOTYROSINE; PROTEIN-TYROSINE-PHOSPHATASE; SALICYLIC ACIDS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES;

EID: 0041842685     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm034088d     Document Type: Article

References (24)

1. For reviews on PTP1B target validation, see: (a) Goldstein, B. J. Protein-Tyrosine phosphate 1B (PTP1B): A Novel Therapeutic Target for Type 2 Diabetes Mellitus, Obesity and Related States of Insulin Resistance. Curr. Drug Targets-Immune Endocr. Metab. Disorders 2001, 1, 265-276. (b) Ukkola, O.; Santaniemi, M. Protein Tyrosine Phosphatase 1B: A New Target for the Treatment of Obesity and Associated Co-Morbidities. J. Intern. Med. 2002, 251, 467-475.
2. For reviews on PTP1B target validation, see: (a) Goldstein, B. J. Protein-Tyrosine Phosphate 1B (PTP1B): A Novel Therapeutic Target for Type 2 Diabetes Mellitus, Obesity and Related States of Insulin Resistance. Curr. Drug Targets-Immune Endocr. Metab. Disorders 2001, 1, 265-276. (b) Ukkola, O.; Santaniemi, M. Protein Tyrosine Phosphatase 1B: A New Target for the Treatment of Obesity and Associated Co-Morbidities. J. Intern. Med. 2002, 251, 467-475.
3. Elchebly, M.; Payette, P.; Michaliszyn, E.; Cromlish, W.; Collins, S.; Loy, A. L.; Normandin, D.; Cheng, A.; Himms-Hagen, J.; Chan, C. C.; Ramachandran, C.; Gresser, M. J.; Tremblay, M. L.; Kennedy, B. P. Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein-Tyrosine Phosphatase-1B Gene. Science 1999, 283, 1544-1548.
4. Klaman, L. D.; Boss, O.; Peroni, O. D.; Kim, J. K.; Martino, J. L.; Zabotny, J. M.; Moghal, N.; Lubkin, M.; Kim, Y.-B.; Sharpe, A. H.; Stricker-Krongrad, A.; Shulman, G. I.; Neel, B. G.; Kahn, B. B. Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice. Mol. Cell. Biol. 2000, 20, 5479-5489.
5. Cheng, A.; Uetani, N.; Simoncic, P. D.; Chaubey, V. P.; Lee-Loy, A.; McGlade, C. J.; Kennedy, B. P.; Tremblay, M. L. Attenuation of Leptin Action and Regulation of Obesity by Protein Tyrosine Phosphatase 1B. Dev. Cell. 2002, 2, 497-503.
6. Zabolotny, J. M.; Bence-Hanulec, K. K.; Stricker-Krongrad, A.; Haj, F.; Wang, Y.; Minokoshi, Y.; Kim, Y. B.; Elmquist, J. K.; Tartaglia, L. A.; Kahn, B. B.; Neel, B. G. PTP1B Regulates Leptin Signal Transduction In Vivo. Dev. Cell. 2002, 2, 489-495.
7. 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, 683-693.
8. For recent reviews on structure-based design of PTP1B inhibitors, see (a) Johnson, T. O.; Ermolieff, J.; Jirousek, M. R. Protein Tyrosine Phosphatase 1B Inhibitors for Diabetes. Nat. Rev. Drug Discovery 2002, 1, 696-709; (b) Liu, G.; Trevillyan, J. M. Protein Tyrosine Phosphatase 1B as a Target for the Treatment of Impaired Glucose Tolerance and Type 2 Diabetes. Curr. Opin. Invest. Drugs 2002, 3, 1608-1616.
9. For recent reviews on structure-based design of PTP1B inhibitors, see (a) Johnson, T. O.; Ermolieff, J.; Jirousek, M. R. Protein Tyrosine Phosphatase 1B Inhibitors for Diabetes. Nat. Rev. Drug Discovery 2002, 1, 696-709; (b) Liu, G.; Trevillyan, J. M. Protein Tyrosine Phosphatase 1B as a Target for the Treatment of Impaired Glucose Tolerance and Type 2 Diabetes. Curr. Opin. Invest. Drugs 2002, 3, 1608-1616.
10. Puius, Y. A.; Zhao, Y.; Sullivan, M.; Lawrence, D. S.; Almo, S. C.; Zhang, Z.-Y. Identification of a Second Aryl Phosphate-Binding Site in Protein-Tyrosine Phosphatase 1B: A Paradigm for Inhibitor Design. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 13420-13425.
11. Szczepankiewicz, B. G.; Liu, G.; Pei, Z.; Xin, Z.; Lubben, T.; Trevillyan, J. M.; Stashko, M. A.; Ballaron, B. J.; Hajduk, P. J.; Liang, H.; Huang, F.; Hutchins, C. W.; Abad-Zapatero, C.; Jirousek, M. R.; Fesik, S. W. Discovery of a Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Based Strategy. J. Am. Chem. Soc. 2003, 125, 4087-4096.
12. Xin, Z.; Oost, T.; Abad-Zapatero, C.; Hajduk, P. J.; Pei, Z.; Szczepankiewicz, B. G.; Hutchins, C. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T.; Trevillyan, J. M.; Jirousek, M. R.; Liu, G. Potent, Selective Inhibitors of Protein Tyrosine Phosphatase 1B. Bioorg. Med. Chem. Lett. 2003, 13, 1887-1890.
13. Shen, K.; Keng, Y. F.; Wu, L.; Guo, X.-L.; Lawrence, D. S.; Zhang, Z.-Y. Acquisition of a Specific and Potent PTP1B Inhibitor from a Novel Combinatorial Library and Screening Procedure. J. Biol. Chem. 2001, 276, 47311-47319.
14. Sun, J.-P.; Fedorov, A. A.; Lee, S.-Y.; Guo, X.-L.; Shen, K.; Lawrence, D. S.; Almo, S. C.; Zhang, Z.-Y. Crystal Structure of PTP1B Complexed with a Potent and Selective Bidentate Inhibitor. J. Biol. Chem. 2003, 278, 12406-12414.
15. 13C-Labeled Methyl Groups. J. Am. Chem. Soc. 2000, 122, 7898-7904.
16. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Discovering High-Affinity Ligands for Proteins: SAR By NMR. Science 1996, 274, 1531-1534.
17. Refined crystallographic coordinates for the structure of PTP1B complexed with compound 6 have been deposited with the Protein Data Bank (www.rcsb.org) with entry codes 1PH0.
18. Iversen, L. F.; Møller, K. B.; Pedersen, A. K.; Peters, G. H.; Petersen, A. S.; Andersen, H. S.; Branner, S.; Mortensen, S. B.; Møller, N. P. H. Structure Determination of T Cell Protein-Tyrosine Phosphatase. J. Biol. Chem. 2002, 277, 19982-19990.
19. Liu, G.; Szczepankiewicz, B. G.; Pei, Z.; Janowick, D.; Xin, Z.; Liang, H.; Hadjuk, P. J.; Abad-Zapatero, C.; Hutchins, C. W.; Fesik, S. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T.; Mika, A. K.; Zinker, B. A.; Trevillyan, J. M.; Jirousek, M. R. Discovery and SAR of Oxalyl-Aryl-Amino Benzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B. J. Med. Chem. 2003, 46, 2093-2103.
20. The actual selectivity would be substantially higher than 75-fold since 3 μM is the highest concentration tested.
21. Yee, S. In Vitro Permeability Across Caco-2 Cells (Colonic) Can Predict In Vivo (Small Intestinal) Absorption in Man-Fact or Myth. Pharm Res. 1997, 14, 763-766.
22. Galetic, I.; Andjelkovic, M.; Meier, R.; Brodbeck, D.; Park, J.; Hemmings, B. A. Mechanism of Protein Kinase B Activation by Insulin/Insulin-Like Growth Factor-1 Revealed by Specific Inhibitors of Phosphoinositide 3-Kinase-Significance for Diabetes and Cancer. Pharmacol. Ther. 1999, 82, 409-425.
23. Bleasdale, J. E.; Ogg, D.; Palazuk, B. J.; Jacob, C. S.; Swanson, M. L.; Wang, X.-Y.; Thompson, D. P.; Conradi, R. A.; Mathews, W. R.; Laborde, A. L.; Stuchly, C. W.; Heijbel, A.; Bergdahl, K.; Bannow, C. A.; Smith, C. W.; Svensson, C.; Liljebris, C.; Schostarez, H. J.; May, P. D.; Stevens, F. C.; Larsen, S. D. Small Molecule Peptidomimetics Containing a Novel Phosphotyrosine Bioisostere Inhibit Protein Tyrosine Phosphatase 1B and Augment Insulin Action. Biochemistry 2001, 40, 5642-5654.
24. Andersen, H. S.; Olsen, O. H.; Iversen, L. F.; Sørensen, A. L. P.; Mortensen, S. B.; Christensen, M. S.; Branner, S.; Hansen, T. K.; Lau, J. F.; Jeppesen, L.; Moran, E. J.; Su, J.; Bakir, F.; Judge, L.; Shahbaz, M.; Collins, T.; Vo, T.; Newman, M. J.; Ripka, W. C.; Møller, N. P. H. Discovery and SAR of a Novel Selective and Orally Bioavailable Nonpeptide Classical Competitive Inhibitor Class of Protein-Tyrosine Phosphatase 1B. J. Med. Chem. 2002, 45, 4443-4459.