MEK162 (ARRY-162, ARRY-438162)
(Synonyms: 贝美替尼,MEK162; ARRY-162; ARRY-438162) 目录号 : GC12843
A MEK1/2 inhibitor
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 | |
| 别名 | 贝美替尼,MEK162; ARRY-162; ARRY-438162 | ||
| 化学名 | 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 | ||
| 分子式 | C17H15BrF2N4O3 | 分子量 | 441.23 |
| 溶解度 | 2mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet