Therapeutic Protease and Peptidase Inhibitors

A special issue of Drugs and Drug Candidates (ISSN 2813-2998). This special issue belongs to the section "Biologics".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 460

Special Issue Editor


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Guest Editor
Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Université Laval, Québec, QC, Canada
Interests: ligands of G protein coupled receptors; receptors for peptide hormones (including bradykinin, anaphylatoxin C5a, neurokinins...); in vitro and in vivo pharmacology (not in silico docking); quantitative assessment of drug antagonism; peptides and peptidomimetics developed as drugs
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Special Issue Information

Dear Colleagues,

The human genome encodes 600–700 proteases (2–3% of genes), defined as hydrolytic enzymes that break down proteins. Digestive proteases were initially characterized, but it was soon understood that proteases mediate many physiological functions in both intra- and extracellular compartments. Protein turnover, autophagy, hormonal maturation and degradation, tissue homeostasis, blood coagulation, cell proliferation, and viral infections are a few examples illustrating the importance of proteases.  Peptidases, which hydrolyze smaller substrates such as peptide hormones, are also of prime physiological importance. Proteases and peptidases belong to diverse families according to their catalytic mechanisms (serine proteases, metalloproteinases/peptidases, cysteine, and aspartic proteases).

Therapeutic inhibitors of proteases and peptidases have increasing importance as drugs, either in the form of small molecules (e.g., angiotensin-converting enzyme inhibitors) or proteins of high specificity. Biologic protease inhibitors exploited in therapeutics include replacement therapy of a deficient or dysfunctional protein (e.g., C1 esterase inhibitor) and engineered inhibitory proteins such as monoclonal antibodies, darpins, and Kunitz domain derivatives. Drugs and Drug Candidates invites submissions for this Special Issue titled "Therapeutic Protease and Peptidase Inhibitors".

Dr. François Marceau
Guest Editor

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Keywords

  • protease inhibitors
  • peptidase inhibitors
  • small molecule protease inhibitors
  • engineered protein inhibitors
  • proteases
  • peptidases

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Published Papers (1 paper)

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Review

8 pages, 392 KB  
Review
Notes on the Physiopathology of the Kinin-Mediated Angioedema Associated with Angiotensin-Converting Enzyme Inhibition
by François Marceau
Drugs Drug Candidates 2026, 5(2), 25; https://doi.org/10.3390/ddc5020025 - 17 Apr 2026
Viewed by 80
Abstract
Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are one of the most successful drug classes for the treatment of hypertension and the prevention of its cardiovascular complications. ACE activates the pressor hormone angiotensin but also inactivates the vasodilator peptide bradykinin (BK). A rare side effect [...] Read more.
Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are one of the most successful drug classes for the treatment of hypertension and the prevention of its cardiovascular complications. ACE activates the pressor hormone angiotensin but also inactivates the vasodilator peptide bradykinin (BK). A rare side effect of ACEis, angioedema (AE), has been proposed to result from pro-inflammatory effects of BK. Novel considerations are offered in this debate: (1) the bradykinin B2 receptor antagonist icatibant has had an inconsistent effect on ACEi-associated AE, but its potency and duration of action are much inferior to those of a novel nonpeptide antagonist of this receptor, deucrictibant. (2) Tissue kallikrein (KLK-1) is an effective kininogenase, particularly abundant in the salivary glands, possibly related to orofacial presentation of ACEi-induced AE. (3) The strongly regulated human kinin B1 receptor, optimally responsive to Lys-des-Arg9-BK, is functionally compartmentalized with KLK-1 which produces Lys-BK from kininogens. Chronic treatment with ACEi drugs in laboratory animals induces the expression of vascular B1R that mediates vasodilation. Therefore, ACEi-AE may be largely or completely initiated by KLK-1. Inhibitors of this protease or combined antagonists of both kinin receptor subtypes may be useful for the management of this condition. Full article
(This article belongs to the Special Issue Therapeutic Protease and Peptidase Inhibitors)
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