MEK162 (ARRY-162, ARRY-438162) (Synonyms: ARRY-438162, MEK162) |
| رقم الكتالوجGC12843 |
MEK162 (ARRY-162 ، ARRY-438162) (MEK162) هو مثبط MEK1 / 2 شفهي وانتقائي. MEK162 (ARRY-162 ، ARRY-438162) (MEK162) يثبط MEK مع IC50 من 12 نانومتر.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 606143-89-9
Sample solution is provided at 25 µL, 10mM.
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MEK162 (ARRY-162, ARRY-438162) is a novel, selective inhibitor of MEK 1/2 with IC50 of about 12 nM [1].
Co-treatment of MEK162 and PKC inhibitors persistently inhibited MAP-kinase pathway. The co-treatment can halt proliferation and induce apoptosis of uveal melanoma cells even with GNAQ or GNA11 mutations [2]. All N-RAS mutant melanoma cells were sensitive to MEK 162. MEK162 reduced ERK1/2 phosphorylation, clonogenic survival, and induced apoptosis [3].
Phase Ib or II clinical trials were conducted in 32 cutaneous melanoma patients. 20 patients in MEK162 monotherapy and 12 on MEK162 plus RAF inhibitor or selective BRAF inhibitor combination therapy underwent ophthalmological examinations and multimodal imaging. These therapy all induced transient retinopathy with multiple bilateral lesions in some patients. The effect of MEK162 in retinopathy has been usually mild, self-limiting, and tolerable [4].
References:
[1]. Jed Pheneger, Eli Wallace, Allison Marlow, Brian Hurley, Joe Lyssikatos, Alison M. Bendele, Patrice A. Lee1. Array BioPharma, Boulder, CO; Bolder BioPath, Boulder, CO. Characterization of ARRY-438162, a potent MEK inhibitor in combination with Methotrexate or Ibuprofen in vivo models of arthritis. American college of rheumatology. 2006 Annual Scientific Meeting.
[2]. Chen X, Wu Q, Tan L, Porter D, Jager MJ, Emery C, Bastian BC. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene. 2013 Oct 21.
[3]. Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Mol Cancer. 2014 Mar 4;13:45.
[4]. Urner-Bloch U, Urner M, Stieger P, Galliker N, Winterton N, Zubel A, Moutouh-de Parseval L, Dummer R, Goldinger SM. Transient MEK inhibitor-associated retinopathy in metastatic melanoma. Ann Oncol. 2014 May 26. pii: mdu169.
| Cell experiment [1]: | |
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Cell lines |
WT (YUVON and YUROB), B-RAF mutant (YUKSI and YUMAC) and N-RAS mutant (YUDOSO and YUKIM) cells |
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Preparation method |
The solubility of this compound in DMSO is >22.1mg/mL. 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. |
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Reacting condition |
10-1000 nM; 4 and 24 hours |
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Applications |
Compared to sensitive cultures (YUROB, YUMAC, YUDOSO, YUKIM), in the MEK162 resistant melanoma cultures (YUVON and YUKSI), the baseline level of phospho-ERK1/2 and the ratio of phospho-ERK1/2 to total ERK1/2 was lower. In MEK162-sensitive melanomas, MEK162 significantly decreased the level of ERK1/2 phosphorylation and clonogenic survival, and induced apoptosis. |
| Animal experiment [2]: | |
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Animal models |
Rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models |
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Dosage form |
CIA studies: 0.3, 1 or 3 mg/kg ARRY-438162 (PO, BID) with or without 30 mg/kg ibuprofen (PO, QD) for six days.AIA model: 1, 3 or 10 mg/kg ARRY-438162 (PO, QD) beginning on day 8 and continuing for 6 days, with or without the addition of 0.05 mg/kg methotrexate (PO, QD) which was dosed days 0-13. |
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Application |
In rat collagen-induced arthritis (CIA) model, ARRY-438162 inhibited increases in ankle diameter by 27% and 50% at 1 and 3 mg/kg, while ibuprofen had 46% inhibition. When combined with ibuprofen, these same two doses resulted in 74% and 72% inhibition, respectively and also inhibited joint destruction by 54% and 77%, respectively. In AIA model, when combined with MTX, 3 and 10 mg/kg of ARRY-438162 inhibited ankle diameter by 55% and 71%, respectively. |
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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. |
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References: [1]. Thumar J, Shahbazian D, Aziz SA, Jilaveanu LB, Kluger HM. MEK targeting in N-RAS mutated metastatic melanoma. Mol Cancer. 2014 Mar 4;13:45. [2]. Jed Pheneger, Eli Wallace, Allison Marlow, Brian Hurley, Joe Lyssikatos, Alison M. Bendele, Patrice A. Lee1. Array BioPharma, Boulder, CO; Bolder BioPath, Boulder, CO. Characterization of ARRY-438162, a potent MEK inhibitor in combination with Methotrexate or Ibuprofen in vivo models of arthritis. American college of rheumatology. 2006 Annual Scientific Meeting. |
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| Cas No. | 606143-89-9 | SDF | |
| المرادفات | ARRY-438162, MEK162 | ||
| Chemical Name | 6-(4-bromo-2-fluoroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide | ||
| Canonical SMILES | CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO | ||
| Formula | C17H15BrF2N4O3 | M.Wt | 441.23 |
| الذوبان | 2mg/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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2664 mL | 11.332 mL | 22.6639 mL |
| 5 mM | 0.4533 mL | 2.2664 mL | 4.5328 mL |
| 10 mM | 0.2266 mL | 1.1332 mL | 2.2664 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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 30 reference(s) in Google Scholar.)
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