SGK1 Inhibition
Targeting a genetically validated disease node to reverse stress-induced disease biology.
OUR SCIENTIFIC APPROACH
A stress-activated disease node
Serum- and glucocorticoid-regulated kinase 1 (SGK1) responds to cellular stress. Research to date has implicated chronic SGK1 activation in cardiovascular diseases associated with abnormal electrical and structural changes.
Thryv is developing highly potent, best-in-class SGK1 inhibitors to address the underlying disease biology and residual risk in rare and common cardiac and cardiometabolic diseases, beginning with Long QT Syndrome and heart failure.
CARDIAC FOCUS
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SGK1 dysregulates cardiac ion channel regulation and electrical activity. SGK1 activation heightens the risk of serious abnormal heart rhythms.
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SGK1 signals pathways of inflammation, tissue remodeling/fibrosis, and metabolism that adversely affect cardiac structure and function.
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Thryv’s best-in-class SGK1 inhibitors are in development for high unmet need cardiac and non-cardiac diseases.
Human genetic validation
Lower ventricular SGK1 expression is associated with reduced heart failure risk.
In the UK Biobank, a rare SGK1 variant was significantly associated with heart failure.
These human genetic findings validate SGK1 as a core disease node to target persistent electrical, functional, and structural disease abnormalities in heart failure and cardiomyopathies.