GSK 650394 |
| Catalog No.GC15441 |
SGK1 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 890842-28-1
Sample solution is provided at 25 µL, 10mM.
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GSK 650394 is a small molecule inhibitor of serum and glucocorticoid-regulated kinase 1 (SGK1) with IC50 value of 13nM [1].
Sgk1 gene is a target gene of androgen. Knockdown of SGK1 expression attenuates androgen-mediated growth of the prostate cancer cell line. Thus, the inhibition of SGK1 is a novel mechanism for the treatment of prostate cancer. GSK 650394 is a competitive inhibitor of SGK1. It shows potent inhibitory activity against the purified SGK1 with IC50 value of 13nM in a fluorescence polarization assay. In the activity-based scintillation proximity assay, GSK 650394 prevents the phosphorylation activity of SGK1 and SGK2 with IC50 values of 62nM and 103nM, respectively. Moreover, GSK 650394 suppresses the androgen-mediated increase of Nedd4-2 phosphorylation in LNCaP cells. It also significantly inhibits cell growth stimulated by androgen with IC50 value of about 1μM [1].
References:
[1] Sherk A B, Frigo D E, Schnackenberg C G, et al. Development of a small-molecule serum-and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer research, 2008, 68(18): 7475-7483.
| Kinase experiment [1]: | |
|
Scintillation proximity assay (SPA) |
SGK1 S422D (60-431 aa; 0.275 μg/mL final concentration) or SGK2 (0.875 μg/mL final concentration) were activated by PDK1 (1.1 μg/mL final concentration) in a buffer consisting of 50 mM Tris (pH 7.5), 0.1 mM EGTA, 0.1 mM EDTA, 10 mM MgCl2, 0.1% β-mercaptoethanol, 1 mg/mL BSA, and ATP (final concentration of 0.15 mM) and incubated for 30 mins at 30 °C. SGK2 was prepared exactly as described for SGK1, except it corresponded to the full-length protein. A solution containing biotinylated CROSStide peptide at a final concentration of 75 μM and γ32P-ATP corresponding to 2 × 106 cpm was prepared in the reaction buffer. In a 96-well plate, 5 μL of GSK 650394 was added to 25 μL of the activated enzyme mixture. To this, 20 μL of the CROSStide mixture was added and incubated for 1 hr at room temperature. Next, 50 μL of a 25 mg/mL slurry of streptavidin-coated SPA beads in PBS with 0.1 M EDTA, pH 8.0 was added. The plate was then sealed and centrifuged for 8 mins at 2000 rpm, and the signal was detected by measuring for 30 sec/well in a Packard TopCount NXT Scintillation Counter. The IC50 values of the inhibition of SGK1 and SGK2 activities by GSK 650394 were calculated from these data using GraphPad Prism 3 Software. |
| Cell experiment [1]: | |
|
Cell lines |
LNCaP cells |
|
Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
~ 10 μM; 7 days |
|
Applications |
In LNCaP cells, GSK 650394 inhibited androgen-mediated enhancement of Nedd4-2 phosphorylation. In addition, GSK 650394 also significantly inhibited androgen-stimulated growth of LNCaP cells, with an IC50 value of ~ 1 μM. |
|
References: [1]. Sherk A B, Frigo D E, Schnackenberg C G, et al. Development of a small-molecule serum-and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer research, 2008, 68(18): 7475-7483. | |
| Cas No. | 890842-28-1 | SDF | |
| Chemical Name | 2-cyclopentyl-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid | ||
| Canonical SMILES | C1CCC(C1)C2=C(C=CC(=C2)C3=CNC4=NC=C(C=C34)C5=CC=CC=C5)C(=O)O | ||
| Formula | C25H22N2O2 | M.Wt | 382.45 |
| Solubility | ≥ 19.1mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6147 mL | 13.0736 mL | 26.1472 mL |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)
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