BI 1291583: a novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis

• Published in: Inflammation research Vol. 72; no. 8; pp. 1709 - 1717
• Main Authors: Kreideweiss, Stefan, Schänzle, Gerhard, Schnapp, Gisela, Vintonyak, Viktor, Grundl, Marc A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2023; Springer Nature B.V
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bronchiectasis; Bronchus; Cathepsins; Cell activation; Cells (biology); Dermatology; Dipeptidyl-peptidase I; Elastase; Enzymatic activity; Fluorescence; Immunology; Inflammatory diseases; Inhibition; Lavage; Leukocytes (neutrophilic); Lipopolysaccharides; Lung diseases; Lungs; Myelopoiesis; Neurology; Neutrophils; Original Research Paper; Pharmacology/Toxicology; Progenitor cells; Protease; Proteinase; Proteinase 3; Respiratory tract diseases; Rheumatology; Serine proteinase; Surface plasmon resonance; Cathepsin C inhibitor; Bronchiectasis; Preclinical; Neutrophil-derived serine protease activity

Background Airway inflammation in chronic inflammatory lung diseases (e.g. bronchiectasis) is partly mediated by neutrophil-derived serine protease (NSP)/antiprotease imbalance. NSPs are activated during neutrophil myelopoiesis in bone marrow by cathepsin C (CatC; DPP1). CatC is therefore an attract...