| Identification | Back Directory | [Name]
EMD638683 | [CAS]
1181770-72-8 | [Synonyms]
EMD638683
]-2-ethyL
N'-[2-(3,5-DifL
)-2-hydroxyacetyL
-4-hydroxy-3-methyL
EMD 638683;EMD-638683
N'-(2-(3,5-difluorophenyl)-2-hydroxyacetyl)-2-ethyl-4-hydroxy-3-methylbenzohydrazide
Benzeneacetic acid, 3,5-difluoro-α-hydroxy-, 2-(2-ethyl-4-hydroxy-3-methylbenzoyl)hydrazide
3,5-Difluoro-alpha-hydroxybenzeneacetic acid 2-(2-ethyl-4-hydroxy-3-methylbenzoyl)hydrazide | [Molecular Formula]
C18H18F2N2O4 | [MDL Number]
MFCD25541743 | [MOL File]
1181770-72-8.mol | [Molecular Weight]
364.34 |
| Chemical Properties | Back Directory | [Boiling point ]
657.6±55.0 °C(Predicted) | [density ]
1.363±0.06 g/cm3(Predicted) | [storage temp. ]
-10 to -25°C | [solubility ]
insoluble in H2O; ≥18.2 mg/mL in DMSO; ≥45.8 mg/mL in EtOH with gentle warming | [form ]
solid | [pka]
8.68±0.25(Predicted) | [color ]
Off-white to light brown | [InChI]
1S/C18H18F2N2O4/c1-3-13-9(2)15(23)5-4-14(13)17(25)21-22-18(26)16(24)10-6-11(19)8-12(20)7-10/h4-8,16,23-24H,3H2,1-2H3,(H,21,25)(H,22,26) | [InChIKey]
SSNAPUUWBPZGOY-UHFFFAOYSA-N | [SMILES]
CC1=C(C(C(NNC(C(C2=CC(F)=CC(F)=C2)O)=O)=O)=CC=C1O)CC |
| Hazard Information | Back Directory | [Uses]
EMD638683 is a highly selective SGK1 inhibitor, with an IC50 value of 3 μM. | [Biological Activity]
EMD638683 is an orally active and highly selective serum/glucocorticoid-regulated kinase 1 (SGK1) inhibitor (IC50 = 3 μM against HeLa cellular NDRG1 phosphorylation) th at significantly decreased blood pressure in fructose-treated mice but not in control saline-treated or in SGK1-knockout animals (4460 ppm in chow~600 mg/kg/day). EMD638683 promotes radiation-induced suicidal death of CaCo-2 colon tumor cells in vitro (50 μM) and decreases the number of colonic tumors following chemical carcinogenesis in vivo (4460 ppm in chow). | [in vivo]
The colon is significantly longer and the colon weight significantly lower in EMD638683-treated mice than in placebo-treated mice, a finding pointing to an influence of EMD638683 on tumor growth following chemical carcinogenesis. In addition, the stomach weight is significantly lower in the EMD treated group. Most importantly, the number of developing tumors following carcinogenic treatment is significantly blunted by EMD638683 treatment[2]. EMD638683 (20 mg/kg, intragastrically) prevents progression of monocrotaline (MCT)-induced pulmonary vascular remodeling in rats. Hemodynamic characteristics show that EMD638683 treatment attenuates 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) compare to vehicle-dosed controls[3]. | [target]
SGK1 | [IC 50]
SGK1 | [References]
[1] Ackermann TF, et al. EMD638683, a novel SGK inhibitor with antihypertensive potency. Cell Physiol Biochem. 2011;28(1):137-46. DOI:10.1159/000331722
[2] Towhid ST, et al. Inhibition of colonic tumor growth by the selective SGK inhibitor EMD638683. Cell Physiol Biochem. 2013;32(4):838-48. DOI:10.1159/000354486
[3] Xi X, et al. Serum-glucocorticoid regulated kinase 1 regulates macrophage recruitment and activation contributing to monocrotaline-induced pulmonary arterial hypertension. Cardiovasc Toxicol. 2014 Dec;14(4):368-78. DOI:10.1007/s12012-014-9260-4
[4] Zhou H, et al. Inhibition of serum- and glucocorticoid-inducible kinase 1 enhances TLR-mediated inflammation and promotes endotoxin-driven organ failure. FASEB J. 2015 Sep;29(9):3737-49. DOI:10.1096/fj.15-270462 |
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