Adenine derivatives invert high glucose-induced thioredoxin-interacting protein overexpression

Chem Biol Drug Des. 2018 Dec;92(6):1998-2008. doi: 10.1111/cbdd.13371. Epub 2018 Sep 11.


Overexpression of thioredoxin-interacting protein (TXNIP) is associated with reduced insulin sensitivity and β-cell apoptosis. We have previously shown that W2476 inhibited high glucose-induced TXNIP expression at both mRNA and protein levels in INS-1E cells. In this study, we describe structural modification and optimization of W2476 leading to three more active derivatives, 8d, 8g, and 9h, capable of suppressing TXNIP expression in BG73 and INS-1E cells, increasing insulin production, and reducing high glucose-induced apoptosis in INS-1E cells.

Keywords: adenine derivative; structural optimization; thioredoxin-binding protein-2; thioredoxin-interacting protein; vitamin D3-upregulated protein-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Down-Regulation / drug effects*
  • Glucose / pharmacology*
  • Inhibitory Concentration 50
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Rats
  • Structure-Activity Relationship


  • Carrier Proteins
  • Cell Cycle Proteins
  • Insulin
  • TXNIP protein, rat
  • Glucose
  • Adenine