Safe and Orally Bioavailable Inhibitor of Serine Palmitoyltransferase Improves Age-Related Sarcopenia.

ABSTRACT: The accumulation of ceramides and related metabolites has emerged as a pivotal mechanism contributing to the onset of age-related diseases. However, small molecule inhibitors targeting the ceramide de novo synthesis pathway for clinical use are currently unavailable. We synthesized a safe and orally bioavailable inhibitor, termed ALT-007, targeting the rate-limiting enzyme of ceramide de novo synthesis, serine palmitoyltransferase (SPT). In a mouse model of age-related sarcopenia, ALT-007, administered through the diet, effectively restored muscle mass and function compromised by aging. Mechanistic studies revealed that ALT-007 enhances protein homeostasis in Caenorhabditis elegans and mouse models of aging and age-related diseases, such as sarcopenia and inclusion bod

SUBMITTER: Poisson J 

PROVIDER: S-EPMC11729425 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature