GDC-0623 (Synonyms: RG 7421; MEK inhibitor 1) |
Catalog No.GC14247 |
MEK1 inhibitor, potent and ATP-uncompetitive
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1168091-68-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment [1]: | |
In vitro Kinase assays |
0.14 μM of purified inactive recombinant MEK-1 protein is preincubated with inhibitors in 15 μL of kinase buffer including (20 mM MOPS pH7.2, 25 mM beta glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM DTT, 100 μM ATP, 15 mM MgCl2). After incubating 10 minutes at 30°C, 1 ng of BRAF, CRAF or BRAF V600E combined with 0.5 μg of inactive recombinant ERK2 is added to the reaction in total volume of 20 μL. After incubating 30 minutes at 30°C the reaction is stopped by adding Laemmle sample buffer. Enzyme activity is measured by determining level of phosphor-MEK by SDS-PAGE. Immunoreactive proteins are visualized with SuperSignal West Pico Chemiluminescent Substrate. |
Cell experiment [1, 2]: | |
Cell lines |
KRAS mutant HCT116 or SW620 cells |
Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reacting condition |
0.01-0.15 μmol/L; 3h-48 h; |
Applications |
GDC-0623 dose- and time-dependently up-regulated the pro-apoptotic BH3-only protein BIM in HCT116 cells or KRAS mutant HCT116 or SW620 cells. GDC-0623 inhibited cellular proliferation with EC50 values of 4 nM, 53 nM, 11 nM, 18 nM and 94 nM for A375 (BRAFV600E), HCT116 (KRASG13D), COLO 205, HT-29, and HCT116 cells, respectively. |
Animal experiment [1]: | |
Animal models |
Mice bearing A375, MiaPaCa-2, and HCT116 xenografts |
Dosage form |
40 mg/kg, oral gavage (PO), by mouth once a day, for 20 days |
Applications |
GDC-0623 showed tumour growth inhibition of 120% and 115% in MiaPaCa-2 and HCT116 xenografts tumour models, respectively. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: 1. Hatzivassiliou, G., Haling, J. R., Chen, H., Song, K., Price, S., Heald, R., Hewitt, J. F., Zak, M., Peck, A., Orr, C., Merchant, M., Hoeflich, K. P., Chan, J., Luoh, S. M., Anderson, D. J., Ludlam, M. J., Wiesmann, C., Ultsch, M., Friedman, L. S., Malek, S. and Belvin, M. (2013) Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers. Nature. 501, 232-236 2. Zaanan, A., Okamoto, K., Kawakami, H., Khazaie, K., Huang, S. and Sinicrope, F. A. (2015) The Mutant KRAS Gene Up-regulates BCL-XL Protein via STAT3 to Confer Apoptosis Resistance That Is Reversed by BIM Protein Induction and BCL-XL Antagonism. J Biol Chem. 290, 23838-23849 |
GDC-0623 is a potent and ATP-uncompetitive inhibitor of MEK1 with Ki value of 0.13nM [1].
GDC-0623 is an allosteric MEK inhibitor and has efficacy against both mutant BRAF and mutant KRAS. In the cell viability assays, GDC-0623 inhibits BRAF (V600E) and KRAS (G13D) with EC50 values of 7nM and 42nM, respectively in A375 cells and HCT116 cells. Besides that, GDC-0623 shows similar efficacy in the two genotypes in a panel of BRAF and KRAS-mutant cancer cell lines. GDC-0623 is found to prevent MEK phosphorylation in cells, resulting in more effective inhibition of pERK. Furthermore, it is found that GDC-0623 blocks RAF activation through the effect on MEK. It induces dimerization of MEK with both BRAF and CRAF and stabilizes the RAF–MEK complex. In addition, GDC-0623 also suppresses RAF activation via inhibiting the formation of BRAF–CRAF heterodimer and the translocation of RAF in plasma membrane [1].
References:
[1] Hatzivassiliou G, Haling J R, Chen H, et al. Mechanism of MEK inhibition determines efficacy in mutant KRAS-versus BRAF-driven cancers. Nature, 2013, 501(7466): 232-236.
Cas No. | 1168091-68-6 | SDF | |
Synonyms | RG 7421; MEK inhibitor 1 | ||
Chemical Name | 5-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)imidazo[1,5-a]pyridine-6-carboxamide | ||
Canonical SMILES | C1=CC(=C(C=C1I)F)NC2=C(C=CC3=CN=CN32)C(=O)NOCCO | ||
Formula | C16H14FIN4O3 | M.Wt | 456.21 |
Solubility | ≥ 16.85mg/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. |
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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 | 2.192 mL | 10.9599 mL | 21.9197 mL |
5 mM | 0.4384 mL | 2.192 mL | 4.3839 mL |
10 mM | 0.2192 mL | 1.096 mL | 2.192 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.)
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.
Average Rating: 5
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