Sulfonated Nonsaccharide Heparin Mimetics Are Potent and Noncompetitive Inhibitors of Human Neutrophil Elastase.

ABSTRACT: Human neutrophil elastase (HNE) is a serine protease that plays vital roles in inflammation, innate immune response, and tissue remodeling processes. HNE has been actively pursued as a drug target, particularly for the treatment of cardiopulmonary diseases. Although thousands of molecules have been reported to inhibit HNE, yet very few are being evaluated in early clinical trials, with sivelestat as the only approved HNE inhibitor. We report here a novel chemotype of sulfonated nonsaccharide heparin mimetics as potent and noncompetitive inhibitors of HNE. Using a chromogenic substrate hydrolysis assay, 14 sulfonated nonsaccharide heparin mimetics were tested for their inhibitory activity against HNE. Only 12 molecules inhibited HNE with IC₅₀ values of 0.22-88.3 μM. The inhibitio

SUBMITTER: Al-Horani RA 

PROVIDER: S-EPMC8154244 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature