Cathepsin C : structure, function, and pharmacological targeting

Stojkovska, Milena (author), Novinec, Marko (author)

Cathepsin C is a papain-like cysteine peptidase known primarily for its involvement in the activation of serine peptidases in neutrophils and other immune cells. Its critical role in this process qualifies cathepsin C as a target for the treatment of inflammatory diseases, and its most advanced inhibitor, brensocatib (Insmed), is currently in phase 3 clinical trials for the treatment of non-cystic fibrosis bronchiectasis. Beyond neutrophils, its importance is highlighted by loss-of-function mutations that cause the recessively inherited Papillon-Lefèvre syndrome. At the molecular level, cathepsin C has several structural and functional features that set it apart from other members of the family and enable its selective targeting. It possesses dipeptidyl-peptidase activity (its other common name is dipeptidyl-peptidase I) due to the presence of an additional exclusion domain that also controls its stepwise tetramerization during maturation. In this review article, we summarize the current state of the art regarding the biochemical properties of cathepsin C, its physiological and pathological roles in neutrophils and beyond, and recent advances in the development and evaluation of cathepsin C inhibitors.

• Language: English
• Keywords: dipeptidyl-peptidase I, DPPI, cysteine catepsin, bronchiectasis, brensocatib
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Publication date: 01.01.2023
• Year: 2023
• Number of pages: Str. 1-17
• Numbering: Vol. 2, iss. 3, art. 14
• PID: 20.500.12556/RUL-148208
• UDC: 547.112
• ISSN on article: 2771-2893
• DOI: 10.20517/rdodj.2023.09
• COBISS.SI-ID: 160356355
• Publication date in RUL: 02.08.2023

Record is a part of a journal

• Title: Rare disease and orphan drugs journal
• Shortened title: Rare dis. orphan drug j.
• Publisher: OAE Publishing Inc.
• ISSN: 2771-2893
• COBISS.SI-ID: 160332035

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: dipeptidil-peptidaza I, DPPI, cisteinski katepsin, bronhiektazija, brensocatib

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: N1-0211
• Name: Uvedba kooperativnosti v peptidaze za izboljšanje njihove aktivnosti in uravnavanja

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0179
• Name: Napredna organska sinteza in kataliza