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| Targets |
EMD638683 S-Form selectively targets serum- and glucocorticoid-regulated kinase 1 (SGK1). SGK1 is a member of the AGC kinase family and is activated downstream of PI3K signaling via phosphorylation by PDK1 and mTORC2. SGK1 regulates numerous cellular processes including epithelial sodium channel (ENaC) activity, which controls sodium reabsorption in the kidney and thus blood pressure. SGK1 also modulates cell cycle progression, apoptosis, and fibrotic responses through phosphorylation of downstream substrates such as NDRG1, FOXO3a, and GSK3beta. Overexpression of SGK1 has been implicated in hypertension, cardiac hypertrophy, renal fibrosis, and tumor progression. EMD638683 is highly selective for SGK1 with an IC₅0 of 3 microM.
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| ln Vitro |
In vitro, EMD638683 (the racemic or enantiomeric forms) inhibits SGK1 kinase activity with an IC₅0 of 3 microM. The compound has been evaluated in human cervical carcinoma HeLa cells by measuring SGK1-dependent phosphorylation of its downstream target NDRG1. EMD638683 concentration-dependently reduces NDRG1 phosphorylation, confirming cellular target engagement. The compound exhibits high selectivity for SGK1 over other AGC kinases including PKB/Akt, PKA, and PKC. The S-form may show slightly different potency compared to the R-form or racemic mixture, depending on the stereospecificity of binding interactions within the kinase active site. Cellular assays confirm that EMD638683 effectively inhibits SGK1-mediated signaling pathways in various cell types.
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| ln Vivo |
In vivo, EMD638683 has been studied in animal models to assess its effects on renal function and electrolyte balance. In rodent studies, EMD638683 administration tended to increase fluid intake and urinary sodium excretion, significantly increased urinary flow rate, and significantly decreased body weight. These physiological effects are consistent with SGK1 inhibition in the kidney, which reduces ENaC-mediated sodium reabsorption, leading to natriuresis and diuresis. The compound has been proposed as a potential lead for counteracting hypertension, particularly in individuals with type 2 diabetes or metabolic syndrome where SGK1 is upregulated. The S-form may exhibit different in vivo potency, bioavailability, or half-life compared to the R-form.
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| Enzyme Assay |
In vitro enzyme assays for EMD638683 S-Form involve measuring SGK1 kinase activity using recombinant human SGK1 enzyme. The assay is performed in kinase buffer with ATP and a peptide substrate (e.g., a biotinylated peptide derived from NDRG1 or a generic kinase substrate). Serial dilutions of EMD638683 S-Form (0.001-100 microM) are incubated with the enzyme and substrate at 30degC for 30-60 minutes. Kinase activity is quantified by measuring phosphorylated substrate using fluorescence polarization, HTRF, or luminescence-based detection (ADP-Glo assay). IC₅0 values are calculated from dose-response curves using nonlinear regression. Selectivity is assessed by screening against a panel of related kinases to confirm specificity for SGK1.
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| Cell Assay |
Cellular assays for EMD638683 S-Form are performed using cell lines expressing SGK1 such as HeLa, HEK293, or MCF-7 cells. Cells are cultured in appropriate medium and seeded in multi-well plates. Following serum starvation for 4-16 hours, cells are treated with serial dilutions of EMD638683 (0.1-100 microM) for 2-24 hours. SGK1 activity is assessed by Western blotting using phospho-specific antibodies against NDRG1 (Ser328) or other SGK1 substrates. Alternatively, cells transfected with a SGK1-responsive luciferase reporter construct can be used. Cell viability, proliferation, and apoptosis are evaluated using standard assays. Concentration-response curves are generated and IC₅0 values for cellular activity are calculated.
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| Animal Protocol |
In vivo animal studies for EMD638683 have been conducted in rodents to evaluate effects on fluid balance and blood pressure. Male Sprague-Dawley rats or mice are administered EMD638683 via oral gavage or intraperitoneal injection at doses ranging from 10-50 mg/kg. Animals are housed in metabolic cages for urine collection over 24-hour periods. Urine volume, electrolyte concentrations (Na+, K+, Cl-), and osmolality are measured. Blood pressure is monitored using tail-cuff plethysmography or radiotelemetry. Body weight and food/water intake are recorded daily. At the end of the study, blood and tissue samples (kidney, heart, liver) are collected for pharmacokinetic analysis and biomarker assessment. The S-form and R-form may be compared for stereospecific effects.
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| ADME/Pharmacokinetics |
EMD638683 S-Form (CAS#: 1184940-46-2) has molecular formula C1₈H1₈F2N2O4 and molecular weight 364.34. The compound is a solid powder with purity ≥98%. Storage: powder at -20degC for long-term storage. The compound is soluble in DMSO. The S-form is one of two enantiomers of EMD638683, and the individual enantiomers may have different pharmacokinetic properties including absorption, protein binding, metabolism, and elimination due to stereospecific interactions with CYP450 enzymes and transporters. The compound is intended for research use only and is not for human therapeutic applications.
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| Toxicity/Toxicokinetics |
Toxicological information for EMD638683 S-Form is limited as the compound is a research chemical. Based on its mechanism of SGK1 inhibition, potential toxicities may include electrolyte imbalances (hypokalemia, hyponatremia), hypotension, and renal effects due to altered sodium handling. The compound should be handled with appropriate laboratory safety precautions including the use of personal protective equipment (gloves, safety goggles, lab coat) and working in a well-ventilated fume hood. Avoid inhalation, ingestion, and skin contact. In case of accidental exposure, rinse with water and seek medical attention if necessary. The compound should be stored desiccated at -20degC and disposed of according to institutional guidelines for hazardous waste.
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| References | |
| Additional Infomation |
EMD638683 S-Form (CAS#: 1184940-46-2) is a highly selective SGK1 inhibitor with an IC₅0 of 3 microM, representing the (S)-enantiomer of the compound. SGK1 is a therapeutic target for hypertension, diabetic nephropathy, fibrosis, and cancer. EMD638683 has been investigated as a potential template for drugs counteracting hypertension in individuals with type 2 diabetes. The compound is supplied as a research chemical for laboratory use only. The availability of both R- and S-forms allows for stereospecific studies of SGK1 inhibition, enabling researchers to investigate the role of chirality in target engagement, potency, and pharmacokinetics. As of the current date, EMD638683 and its enantiomers remain preclinical research compounds and have not been approved for any clinical indication.
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| Molecular Formula |
C₁₈H₁₈F₂N₂O₄
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| Molecular Weight |
364.34
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| Exact Mass |
364.123
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| CAS # |
1184940-46-2
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| Related CAS # |
EMD638683;1181770-72-8;EMD638683 R-Form;1184940-47-3
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| PubChem CID |
66577017
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| Appearance |
Off-white to pink solid powder
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| LogP |
3.267
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
498
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCC1=C(C=CC(=C1C)O)C(=O)NNC(=O)[C@H](C2=CC(=CC(=C2)F)F)O
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| InChi Key |
SSNAPUUWBPZGOY-INIZCTEOSA-N
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| InChi Code |
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)/t16-/m0/s1
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| Chemical Name |
N'-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]-2-ethyl-4-hydroxy-3-methylbenzohydrazide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~274.47 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7447 mL | 13.7234 mL | 27.4469 mL | |
| 5 mM | 0.5489 mL | 2.7447 mL | 5.4894 mL | |
| 10 mM | 0.2745 mL | 1.3723 mL | 2.7447 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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