Bicyclic benzofuran and indole-based salicylic acids as protein tyrosine phosphatase inhibitors

Yantao He, Li Fan Zeng, Zhi Hong Yu, Rongjun He, Sijiu Liu, Zhong Yin Zhang

Research output: Contribution to journalArticle

30 Scopus citations


Protein tyrosine phosphatases (PTPs) constitute a large and structurally diverse family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. Malfunction of PTP activity has significant implications in many human diseases, and the PTP protein family provides an exciting array of validated diabetes/obesity (PTP1B), oncology (SHP2), autoimmunity (Lyp), and infectious disease (mPTPB) targets. However, despite the fact that PTPs have been garnering attention as novel therapeutic targets, they remain largely an untapped resource. The main challenges facing drug developers by the PTPs are inhibitor specificity and bioavailability. Work over the last ten years has demonstrated that it is feasible to develop potent and selective inhibitors for individual members of the PTP family by tethering together small ligands that can simultaneously occupy both the active site and unique nearby peripheral binding sites. Recent results with the bicyclic salicylic acid pharmacophores indicate that the new chemistry platform may provide a potential solution to overcome the bioavailability issue that has plagued the PTP drug discovery field for many years. Structural analysis of PTP-inhibitor complexes reveals molecular determinants important for the development of more potent and selective PTP inhibitors, thus offering hope in the medicinal chemistry of a largely unexploited protein class with a wealth of attractive drug targets.

Original languageEnglish (US)
Pages (from-to)1940-1946
Number of pages7
JournalBioorganic and Medicinal Chemistry
Issue number6
StatePublished - Mar 15 2012


  • Bioavailability
  • Combinatorial chemistry
  • Inhibitor specificity
  • Protein tyrosine phosphatases
  • Salicylic acid
  • Therapeutic target

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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