Work

Genetic, Preclinical, and Clinical Evidence Supports SGK1 Inhibition in Heart Failure

Year: 2026

Type: article

Abstract: H eart failure (HF) carries substantial morbidity and mortality despite guidelinedirected medical therapy (GDMT), and residual risk persists after hospitalization for HF with reduced ejection fraction (EF).1,2 Novel strategies addressing myocardial metabolic stress, inflammation, fibrosis, and electrical remodeling are needed.3 Serum/glucocorticoid-regulated kinase 1 (SGK1) is a stress-responsive kinase implicated in pathological structural and electrical remodeling across these domains, but translation has been limited by the lack of selective inhibitors.4,5 Here we present convergent evidence establishing SGK1 target validity through human genetics and cardiac transcriptomics, demonstrating preclinical efficacy in a pressure-overload model, and reporting safety and pharmacodynamic engagement from phase 1 clinical studies.

Source: JACC Heart Failure

DOI: 10.1016/j.jchf.2026.103304