EMD638683 is a selective SGK1 inhibitor. EMD638683 suppresses the phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1), with an IC50 value of 3.35±0.32 μM in the cell culture medium. Additionally, EMD638683 exhibits inhibitory activity against cAMP-dependent protein kinase (PKA), mitogen- and stress-activated protein kinase 1 (MSK1), protein kinase C-related kinase 2 (PKR2), as well as the SGK isoforms SGK2 and SGK3 [1]. In both control and EMD638683 (50 μM)-treated CaCo-2 cells, radiation significantly elevates the proportion of cells undergoing late apoptosis. Treatment with EMD638683 alone tends to increase the percentage of apoptotic CaCo-2 cells. Post-radiation, the proportion of apoptotic EMD638683-treated CaCo-2 cells is notably higher than that of apoptotic control cells. Therefore, EMD638683 treatment substantially enhances apoptosis following radiation [2].
体内研究
The colon length is markedly extended, and the colon weight is significantly reduced in mice treated with EMD638683 compared to those treated with a placebo, suggesting an impact of EMD638683 on tumor growth subsequent to chemical carcinogenesis. Furthermore, the stomach weight is significantly lower in the EMD-treated group. Notably, EMD638683 treatment significantly suppresses the development of tumors following carcinogenic treatment [2].
EMD638683 administration (20 mg/kg, intragastrically) prevents the progression of monocrotaline (MCT)-induced pulmonary vascular remodeling in rats. Hemodynamic parameters indicate that EMD638683 treatment reduces right ventricular systolic pressure (RVSP) (15.8±2.5 vs. 28.2±3.1 mmHg; P<0.05; n=6) and right ventricular hypertrophy index (RVHI) (0.27±0.02 vs. 0.41±0.06; P<0.05; n=6) compared to vehicle-treated controls [3].
体外研究
EMD638683 is a selective SGK1 inhibitor. EMD638683 suppresses the phosphorylation of NDRG1 (N-Myc downstream-regulated gene 1), with an IC50 value of 3.35±0.32 μM in the cell culture medium. Additionally, EMD638683 exhibits inhibitory activity against cAMP-dependent protein kinase (PKA), mitogen- and stress-activated protein kinase 1 (MSK1), protein kinase C-related kinase 2 (PKR2), as well as the SGK isoforms SGK2 and SGK3 [1].
In both control and EMD638683 (50 μM)-treated CaCo-2 cells, radiation significantly elevates the proportion of cells undergoing late apoptosis. Treatment with EMD638683 alone tends to increase the percentage of apoptotic CaCo-2 cells. Post-radiation, the proportion of apoptotic EMD638683-treated CaCo-2 cells is notably higher than that of apoptotic control cells. Therefore, EMD638683 treatment substantially enhances apoptosis following radiation [2].
EMD638683 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse cortical neurons
10 µM
10 min
To evaluate the effect of SGK inhibitors on NMDA currents using gramicidin-perforated patch-clamp recording, results showed that 10 μM EMD638683 significantly inhibited NMDA currents
J Neurochem. 2016 Jul;138(2):354-61.
Mouse cortical neurons
30 µM
10 min
To evaluate the effect of SGK inhibitors on NMDA receptor-mediated neurotoxicity, results showed that EMD638683 significantly inhibited NMDA-induced cell injury and Ca2+ increase
J Neurochem. 2016 Jul;138(2):354-61.
Bone marrow mononuclear cells (BMMCs)
10 µM, 1 µM, 0 µM
14 days
To study the effect of SGK inhibitor EMD638683 on osteoclasts in myeloma patients. Results showed that EMD638683 significantly inhibited the expression of SGK3 and p-SGK3 and reduced the area and resorption function of osteoclasts.
Cancer Biol Med. 2021 May 7;18(3):721–33.
HCT116 cells
25 µM
24 hours
Inhibition of SGK-1 kinase activity, resulting in decreased ATP production and cell viability in ECM-detached cells
Cell Death Differ. 2016 Aug;23(8):1271-82.
MCF-10A cells
25 µM
24 hours
Inhibition of SGK-1 kinase activity, resulting in decreased ATP production and cell viability in ECM-detached cells
Cell Death Differ. 2016 Aug;23(8):1271-82.
Primary human aortic smooth muscle cells (HAoSMCs)
50 µM
24 hours
EMD638683 inhibited phosphate-induced calcification and osteo-/chondrogenic transdifferentiation in HAoSMCs
J Clin Invest. 2018 Jul 2;128(7):3024-3040.
Human aortic smooth muscle cells (HAoSMCs)
50 µM
24 hours
Inhibited high glucose-induced osteogenic transdifferentiation and calcification of HAoSMCs
Int J Mol Sci. 2020 Sep 29;21(19):7207.
MCF-7 breast cancer cells
50 µM
24 hours
Enhanced TAC-induced apoptotic response, activated caspase-3, and promoted early and late apoptosis
Cancer Biol Ther. 2015;16(1):52-9.
Primary murine hepatic stellate cells
1 µM
72 hours
Inhibited Nedd4L phosphorylation, thereby suppressing Smad3 phosphorylation and collagen I production
Gastroenterol Rep (Oxf). 2025 Mar 10;13:goaf022.
EMD638683 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL6 mice
Middle cerebral artery occlusion (MCAO) model
Intracerebroventricular injection
1 mM
Single administration, 30 min before MCAO
To evaluate the effect of SGK inhibitors on ischemic brain injury, results showed that EMD638683 significantly reduced infarct volume
J Neurochem. 2016 Jul;138(2):354-61.
C57/B6 mice
Angiotensin II-induced hypertensive mouse model
Intraperitoneal injection
10 mg/kg
Once daily for 2 weeks
EMD638683 significantly reversed renal dysfunction and cardiac dysfunction in AngII-induced hypertensive mice, reduced renal and cardiac fibrosis, and inhibited Th17/Treg imbalance.
Injected at weeks 1, 3, and 6, lasting for 8 weeks
Inhibited Nedd4L phosphorylation, alleviated liver fibrosis and inflammation, and improved gut microbiota
Gastroenterol Rep (Oxf). 2025 Mar 10;13:goaf022.
Mice
Cholecalciferol overload model
Oral gavage
300 mg/kg
Twice daily for 3 days
EMD638683 significantly reduced aortic calcification and stiffness
J Clin Invest. 2018 Jul 2;128(7):3024-3040.
C57BL/6 mice
Neonatal murine retinal vascularisation model
Oral gavage
600 mg/kg
For a week
Investigate the effect of GJA4 mutation on vascular morphology, results showed that EMD638683 reversed the dilated venous lumen and elevated vascular density caused by GJA4 mutation.
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