SGK1 Inhibition

Why Inhibit SGK1?

Serum and Glucocorticoid Kinase 1 (SGK1) is a signaling hub in many cellular pathways that are activated by a variety of cellular stressors. Evolved to help cells cope with momentary adverse conditions, SGK1 is chronically activated in various disease states and contributes to their progression. SGK1 has been implicated in various cardiovascular conditions, including QT prolongation, heart failure, and atrial fibrillation.

SGK1 & Long QT Syndrome (LQTS)

SGK1 has been shown to modulate cardiac ion channel function and surface expression in the heart. When activated, SGK1 acts on cardiac ion channels, and can result in adverse prolongation of the QT interval, a condition known as Long QT Syndrome (LQTS). SGK1 is involved in both congenital LQTS (caused by genetic mutations) and acquired (drug-induced) Long QT, both of which can lead to the development of lethal heart arrhythmias.

In LQTS, SGK1 inhibition addresses the underlying ion channel pathology responsible for abnormal electrical signaling. Unlike drugs that directly block ion channels and do not address the underlying pathology or involvement of multiple ion channels, SGK1 inhibition may address the underlying pathology due to electrical and structural remodeling of cardiomyocytes.

SGK1 & Heart Failure and Atrial Fibrillation

In cardiometabolic diseases, SGK1 plays a critical role in driving pathological processes, including, inflammation, structural remodeling, electrical remodeling and fibrosis, which can play a significant role in the development of heart failure and atrial fibrillation.  Targeting SGK1 has the potential to comprehensively address these interconnected pathways that drive disease progression.