Update on Mast Cell Proteases as Drug Targets.

Abstract

Mast cell granules are packed with proteases, which are released with other mediators by degranulating stimuli. Several of these proteases are targets of potentially therapeutic inhibitors based on hypothesized contributions to diseases, notably asthma and ulcerative colitis for β-tryptases, heart and kidney scarring for chymases, and airway infection for dipeptidyl peptidase-I. Small-molecule and antibody-based β-tryptase inhibitors showing preclinical promise were tested in early-phase human trials with some evidence of benefit. Chymase inhibitors were given safely in Phase II trials without demonstrating benefits, whereas dipeptidyl peptidase-I inhibitor improved bronchiectasis, in effects likely related to inactivation of the enzyme in neutrophils.

• Authors: George H Caughey
• Journal: Immunology and allergy clinics of North America (Immunol Allergy Clin North Am) Vol. 43 Issue 4 Pg. 777-787 (11 2023) ISSN: 1557-8607 [Electronic] United States
• PMID: 37758413 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Peptide Hydrolases
• Tryptases
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

Topics

• Humans
• Mast Cells
• Peptide Hydrolases (pharmacology)
• Tryptases
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (pharmacology)