EMD638683 (S-Form)

EMD638683 (S-Form) (Compound 1a), the S-enantiomer of EMD638683 (HY-15193), is a SGK1 inhibitor with an IC₅₀ value > 300 nM. EMD638683 is an orally active SGK1 inhibitor with an IC₅₀ of 3 μM. EMD638683 exhibits strong inhibition against SGK1, moderate inhibition against SGK2 and SGK3, and shows excellent selectivity for other AGC kinase family members. EMD638683 has antihypertensive activity by inhibiting SGK1, and independently of the blood pressure-lowering effect, it effectively prevents heart inflammation and fibrosis caused by hypertension by inhibiting the cardiac NLRP3 inflammation body/ IL-1β axis. EMD638683 promotes apoptosis of colon cancer cells and sensitizes radiotherapy. EMD638683 (S-Form) can be used in research related to hypertension, hypertensive heart damage, and colon cancer^[1][2][3][4]. In Vitro:EMD638683 (50 μM; 9-25 h) inhibits NLRP3 inflammasome activation and IL-1β secretion in mouse bone marrow-derived macrophages induced by angiotensin II (Ang II) by targeting NLRP3 expression^[2].
EMD638683 (50 μM; 25-49 h) inhibits angiotensin II-induced transformation of primary mouse cardiac fibroblasts into myofibroblasts by reducing IL-1β secretion from macrophages^[2].
EMD638683 (50 μM; 96 h) enhances radiation-induced apoptotic death of Caco-2 colon cancer cells^[3]. In Vivo:EMD638683 (600 mg/kg, administered via mixed diet for 4 consecutive days) normalizes systolic blood pressure in hyperinsulinemic, salt-loaded wild-type mice, reducing their blood pressure from 111 mmHg to 87 mmHg over the 4-day treatment period^[1].
EMD638683 (600 mg/kg, administered via mixed feed for 4 weeks) prevents hypertension in wild-type mice treated with 10% fructose in isotonic saline for 4 weeks^[1].