Transglutaminase inhibitors: a patent review

Expert Opin Ther Pat. 2016;26(1):49-63. doi: 10.1517/13543776.2016.1115836. Epub 2015 Nov 24.


Introduction: Transglutaminases (TGases) are a class of enzymes that play multifunctional roles. Their protein-crosslinking activity has been linked to fibrosis and Huntington's disease, their glutamine deamidation activity has been related to celiac disease and their GTP-binding activity has been implicated in cancer. All of these physiological disorders have prompted the development of inhibitors, which has accelerated dramatically over the past decade.

Areas covered: This review presents an overview of TGase inhibitors published in the patent literature, from the first compounds developed in the late 1980's, to the current date. This article is focussed on the chemical structure of new inhibitors and their probable mechanism of action.

Expert opinion: Comparison of effective TGase inhibitors reveals common structural features that may guide future design. Many of these elements are embodied in the first TGase inhibitor to recently enter into clinical trials.

Keywords: Factor XIII; Huntington’s disease; TG2; cancer; celiac disease; fibrosis; inhibitors; transglutaminase.

Publication types

  • Review

MeSH terms

  • Animals
  • Celiac Disease / drug therapy
  • Celiac Disease / enzymology
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Huntington Disease / drug therapy
  • Huntington Disease / enzymology
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Patents as Topic
  • Transglutaminases / antagonists & inhibitors*
  • Transglutaminases / metabolism


  • Enzyme Inhibitors
  • Transglutaminases