The design strategy of selective PTP1B inhibitors over TCPTP

Bioorg Med Chem. 2016 Aug 15;24(16):3343-52. doi: 10.1016/j.bmc.2016.06.035. Epub 2016 Jun 18.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) has already been well studied as a highly validated therapeutic target for diabetes and obesity. However, the lack of selectivity limited further studies and clinical applications of PTP1B inhibitors, especially over T-cell protein tyrosine phosphatase (TCPTP). In this review, we enumerate the published specific inhibitors of PTP1B, discuss the structure-activity relationships by analysis of their X-ray structures or docking results, and summarize the characteristic of selectivity related residues and groups. Furthermore, the design strategy of selective PTP1B inhibitors over TCPTP is also proposed. We hope our work could provide an effective way to gain specific PTP1B inhibitors.

Keywords: Design strategy; Diabetes; PTP1B inhibitor; Selectivity; TCPTP.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Hydrogen Bonding
  • Molecular Docking Simulation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1