Tryptase inhibitors: a patent review

Expert Opin Ther Pat. 2017 Aug;27(8):919-928. doi: 10.1080/13543776.2017.1322064. Epub 2017 May 3.

Abstract

Tryptase is one of the main serine-proteinases located in the secretory granules of mast cells, and is released through degranulation, which is involved in the pathogenesis of allergic inflammatory disease, cardiovascular diseases, lung fibrosis and tumor. Therefore, inhibitors targeting tryptase may represent a new direction for the treatment of allergic inflammatory disease and other diseases. Areas covered: In this article, we discussed the history and development of tryptase inhibitors and described a variety of tryptase inhibitors via their structures and biological importance in clinical studies and drug development for tryptase-related diseases. Expert opinion: Initial tryptase inhibitors based on indole structure as the hydrophobic substituent on a benzylamine-piperidine template have low specificity and poor bioavailability. Therefore, designing new and specific inhibitors targeting tryptase should be involved in future clinical studies. Modifications toward indoles with varying N-substitution, introducing an amide bond, and growing the chain length contribute to an increase in the specific selectivity and potency of tryptase inhibitors. Tryptase has become the research hotspot to explore many related diseases. Therefore, there has been growing appreciation for the potential importance of the tryptase inhibitors as a target for treating these diseases.

Keywords: Tryptase; mast cell; specificity; synthetic inhibitors; tryptase-related diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / enzymology
  • Inflammation / drug therapy
  • Inflammation / enzymology
  • Mast Cells / enzymology
  • Mast Cells / metabolism
  • Patents as Topic
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / pharmacology*
  • Tryptases / antagonists & inhibitors*
  • Tryptases / metabolism

Substances

  • Serine Proteinase Inhibitors
  • Tryptases