Preclinical Safety Profile of Deg-AZM, a Clinical-Stage New Transgelin Agonist: hERG Inhibition Study In Vitro, Cardiovascular-Respiratory Pharmacology, and Single/Repeated-Dose Toxicity in Beagle Dogs.

ABSTRACT: Background: Slow transit constipation (STC) represents a refractory gastrointestinal disorder with limited therapeutic options. Deglycosylated azithromycin (Deg-AZM) is a small molecule Transgelin agonist effective against STC, which has been approved for 2024 clinical trials. Objectives: This study comprehensively evaluated the cardiac safety (hERG inhibition), acute cardiovascular-respiratory effects, and single/repeated-dose toxicity of Deg-AZM in Beagle dogs to de-risk clinical translation. Methods: Using automated patch-clamp (hERG-HEK293 cells; 0.1-1000 μM), telemetric monitoring in Beagles (3/8/24 mg/kg; Latin square design), and GLP-compliant toxicity studies (single-dose: 150-300 mg/kg; 28-day: 5-50 mg/kg/day), we assessed functional, biochemical, histopatholo

SUBMITTER: Gu X 

PROVIDER: S-EPMC12467691 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature