Exploration of a Class of Aryl Imidazolyl Ureas As Potent Acid Ceramidase Inhibitors for the Treatment of Fibrotic Diseases.

ABSTRACT: Acid ceramidase (aCDase) is an essential enzyme in sphingolipid metabolism and has been linked to various pathological conditions, including cancer and fibrosis. In our previous studies, we observed that inhibiting aCDase with B13 (4) helped alleviate liver fibrosis in mouse models and in ex vivo human precision-cut liver slices. However, B13 (4) showed limited potency, prompting us to search for more effective aCDase inhibitors. During our exploration of well-established urea-type inhibitors, we discovered that the aryl imidazolyl urea scaffold demonstrated both high potency and chemical stability. Among the tested compounds, compound 43 stood out with its nanomolar IC₅₀ activity against aCDase and its ability to significantly reduce fibrosis markers, such

SUBMITTER: Beresis R 

PROVIDER: S-EPMC12355242 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature