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Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy.

Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, Xin Z, Lubben TH, Trevillyan JM, Stashko MA, Ballaron SJ, Liang H, Huang F, Hutchins CW, Fesik SW, Jirousek MR
J Am Chem Soc 125 4087-96 (2003)
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Cited: 98 times
EuropePMC logo PMID: 12670229

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.

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  1. Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives. Liu R, Mathieu C, Berthelet J, Zhang W, Dupret JM, Rodrigues Lima F. Int J Mol Sci 23 7027 (2022)

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  1. Using chemical shift perturbation to characterise ligand binding. Williamson MP. Prog Nucl Magn Reson Spectrosc 73 1-16 (2013)
  2. A decade of fragment-based drug design: strategic advances and lessons learned. Hajduk PJ, Greer J. Nat Rev Drug Discov 6 211-219 (2007)
  3. Fragment-based lead discovery. Rees DC, Congreve M, Murray CW, Carr R. Nat Rev Drug Discov 3 660-672 (2004)
  4. PTP1B: from the sidelines to the front lines! Tonks NK. FEBS Lett 546 140-148 (2003)
  5. Inhibitors of protein tyrosine phosphatases: next-generation drugs? Bialy L, Waldmann H. Angew Chem Int Ed Engl 44 3814-3839 (2005)
  6. Perspectives on NMR in drug discovery: a technique comes of age. Pellecchia M, Bertini I, Cowburn D, Dalvit C, Giralt E, Jahnke W, James TL, Homans SW, Kessler H, Luchinat C, Meyer B, Oschkinat H, Peng J, Schwalbe H, Siegal G. Nat Rev Drug Discov 7 738-745 (2008)
  7. Fragment-based lead discovery: leads by design. Carr RA, Congreve M, Murray CW, Rees DC. Drug Discov Today 10 987-992 (2005)
  8. Protein tyrosine phosphatases: structure-function relationships. Tabernero L, Aricescu AR, Jones EY, Szedlacsek SE. FEBS J 275 867-882 (2008)
  9. Hit discovery and hit-to-lead approaches. Keseru GM, Makara GM. Drug Discov Today 11 741-748 (2006)
  10. Transforming fragments into candidates: small becomes big in medicinal chemistry. de Kloe GE, Bailey D, Leurs R, de Esch IJ. Drug Discov Today 14 630-646 (2009)
  11. Recent advances in protein tyrosine phosphatase 1B inhibitors. Taylor SD, Hill B. Expert Opin Investig Drugs 13 199-214 (2004)
  12. Biochemical applications of mass spectrometry in pharmaceutical drug discovery. Geoghegan KF, Kelly MA. Mass Spectrom Rev 24 347-366 (2005)
  13. NMR-based screening technologies. Coles M, Heller M, Kessler H. Drug Discov Today 8 803-810 (2003)
  14. Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review. Verma M, Gupta SJ, Chaudhary A, Garg VK. Bioorg Chem 70 267-283 (2017)
  15. Natural compounds as a source of protein tyrosine phosphatase inhibitors: application to the rational design of small-molecule derivatives. Ferreira CV, Justo GZ, Souza AC, Queiroz KC, Zambuzzi WF, Aoyama H, Peppelenbosch MP. Biochimie 88 1859-1873 (2006)
  16. Library screening by fragment-based docking. Huang D, Caflisch A. J Mol Recognit 23 183-193 (2010)
  17. Recent applications of protein crystallography and structure-guided drug design. Williams SP, Kuyper LF, Pearce KH. Curr Opin Chem Biol 9 371-380 (2005)
  18. Bidentate inhibitors of protein tyrosine phosphatases. Low JL, Chai CL, Yao SQ. Antioxid Redox Signal 20 2225-2250 (2014)
  19. Negishi cross-couplings in the synthesis of amino acids. Brittain WDG, Cobb SL. Org Biomol Chem 16 10-20 (2017)
  20. Phosphotyrosine isosteres: past, present and future. Cerulli RA, Kritzer JA. Org Biomol Chem 18 583-605 (2020)
  21. The development of protein tyrosine phosphatase1B inhibitors defined by binding sites in crystalline complexes. Zhang Y, Du Y. Future Med Chem 10 2345-2367 (2018)

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