DEL-22379 |
Catalog No.GC16214 |
DEL-22379 est un inhibiteur de dimérisation ERK. DEL-22379 se lie facilement À ERK2 avec un Kd estimé dans la gamme micromolaire faible, bien que la liaison soit détectable même À de faibles concentrations nanomolaires. La dimérisation de ERK2 est progressivement inhibée avec une IC50 d'environ 0,5 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 181223-80-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | HEK293T cells are plated at a density of 1,000-2,000 cells/well and treated with DEL-22379 (0.2-1 μ M) for 48 hr, Alamar Blue is added, and the colorimetric change is measured at 570 and 600 nm. GI50 is estimated by nonlinear regression using GraphPad5 Prism Software. Apoptosis is analyzed by evaluating caspase 3 activity, either by western blotting or using the Caspase-Glo 3/7 luminogenic assay[1]. |
Animal experiment: | Mice[1]Cancer cells are xenografted in female, athymic nu/nu mice of 8 weeks of age. 3×106 cells are injected subcutaneously in the lateral flank and allowed to develop for 10-15 days before treatment with DEL-22379 at 15 mg/kg every 12 hr for 2 weeks. patient-derived xenografts (PDXs) are performed using patient-derived colorectal cancer cells harboring BRAFV600E from non-necrotic areas of primary adenocarcinomas from patients that undergo surgical resection. Cells are grafted in both flanks or in the cecum of NOD-SCID mice. DEL-22379 is administered by intra-peritoneal injection at a concentration of 15 mg/kg every 12 hr for 30 days[1]. |
References: [1]. Herrero A, et al. Small Molecule Inhibition of ERK Dimerization Prevents Tumorigenesis by RAS-ERK Pathway Oncogenes. Cancer Cell. 2015 Aug 10;28(2):170-82. |
DEL-22379 is an inhibitor of the dimerization of ERK with IC50 values ranging from 150-400 nM regardless of genotypes in oncogenic cells [1].
As an spatial regulator of ERK signals, ERK dimerization is essential. Impeding ERK dimerization can result in the impeding of ERK signals’ extranuclear component and hence result in curtailing tumor development and cellular transformation [1].
In HEK293 cells, DEL-22379 abolished EGF-stimulated ERK dimerization. In these cells, the EGF-induced co-immunoprecipitation of hemagglutinin- or FLAG epitopes- tagged ectopic ERK2 molecules, was abolished by DEL-22379 with an IC50 value of ~0.5 µM. In both assays, the inhibition of DEL-22379 to ERK dimerization was not associated with ERK phosphorylation. In the cytoplasm of EGF-stimulated HeLa cells, ERK dimerization was prominent, but previous treatment with DEL-22379 also resulted in no detected ERK dimmers [1].
In nude mice with some of the aforementioned tumor cell lines, DEL-22379 at a dose of 15 mg/kg inhibited ERK dimerization evidently in xenografted tumors and in liver extracts. DEL-22379 inhibited the tumor progression of A375 cells (BRAF mutant) markedly. Activated-RAS-driven tumors were very sensitive to DEL-22379. Data indicated that tumorigenesis had greater requirements for ERK dimerization than for proliferation. In tumors, treatment with DEL-22379 resulted in extensive mucinous differentiation and cell death [1].
Reference:
[1]. Herrero A, Pinto A, Colón-Bolea P, et al. Small molecule inhibition of ERK dimerization prevents tumorigenesis by RAS-ERK pathway oncogenes. Cancer cell, 2015, 28(2): 170-182.
Cas No. | 181223-80-3 | SDF | |
Chemical Name | N-(3-((5-methoxy-1H-indol-3-yl)methylene)-2-oxoindolin-5-yl)-3-(piperidin-1-yl)propanamide | ||
Canonical SMILES | O=C1NC2=CC=C(NC(CCN3CCCCC3)=O)C=C2C1=CC4=CNC5=CC=C(OC)C=C54 | ||
Formula | C26H28N4O3 | M.Wt | 444.53 |
Solubility | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS(pH 7.2) (1:3): 0.25 mg/ml,Ethanol: slightly soluble | 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. |
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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 | 2.2496 mL | 11.2478 mL | 22.4957 mL |
5 mM | 0.4499 mL | 2.2496 mL | 4.4991 mL |
10 mM | 0.225 mL | 1.1248 mL | 2.2496 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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.)
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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.
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