产品描述: | Binimetinib (MEK162) is an oral and selective MEK1/2 inhibitor. Binimetinib (MEK162) inhibits MEK with an IC50 of 12 nM. |
靶点: |
MEK:12 nM (IC50);Autophagy ;MEK;Autophagy |
体内研究: |
Treatment with Binimetinib (ARRY-438162) reduces disease severity in a dose-related manner in both animal models. ARRY-438162 in the CIA model inhibits increases in ankle diameter by 27% and 50% at 1 and 3 mg/kg, while Ibuprofen has 46% inhibition. When combined with Ibuprofen, these same two doses result in 74% and 72% inhibition, respectively. Microscopic examination of the ankle joints show Binimetinib (ARRY-438162) significantly inhibits lesions (inflammation, cartilage damage, pannus formation and bone resorption) by 32% and 60% at 1 and 3 mg/kg, while treatment with Ibuprofen alone results in 17% inhibition, which is not significantly different from the controls. When these two doses of Binimetinib (ARRY-438162) are combined with ibuprofen, the result is 54% and 77% inhibition of joint destruction. In AIA, 3 and 10 mg/kg of Binimetinib (ARRY-438162) inhibit AIA ankle diameter 11% and 34%, while MTX has 33% inhibition. When combined with MTX, 3 and 10 mg/kg of Binimetinib (ARRY-438162) result in 55% and 71% inhibition. Microscopic examination of ankle joints for inflammation and bone resorption also shows improved efficacy versus either compound alone. When Binimetinib (MEK162) is combined with BEZ235, a significant reduction of tumor growth is observed (P=0.01). This increase in antitumor activity is accompanied by a decrease in phospho-ERK and phospho-S6 staining. No significant changes are observed in phospho-4EBP1 staining, a direct target of mTOR activity |
参考文献: |
1. J Pheneger, et al. 2006, ACR Annual Scientific Meeting. Abst 794. 2. Serra V, et al. RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest, 2013, 123(6), 2551-2563. 3. Kiessling MK, et al. Mutant HRAS as novel target for MEK and mTOR inhibitors. Oncotarget. 2015 Dec 8;6(39):42183-96. 4. Cheng H, et al. PIK3CA(H1047R)- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene. 2016 Jun 9;35(23):2961-70. 5. Seip K, et al. Fibroblast-induced switching to the mesenchymal-like phenotype and PI3K/mTOR signaling protects melanoma cells from BRAF inhibitors. Oncotarget. 2016 Apr 12;7(15):19997-20015. |
溶解性: |
DMSO : 50 mg/mL (113.32 mM; Need ultrasonic) |
保存条件: |
-20℃ |
配置溶液浓度参考: |
|
1mg |
5mg |
10mg |
1 mM |
2.266 ml |
11.332 ml |
22.664 ml |
5 mM |
0.453 ml |
2.266 ml |
4.533 ml |
10 mM |
0.227 ml |
1.133 ml |
2.266 ml |
50 mM |
0.045 ml |
0.227 ml |
0.453 ml |
|
注意: |
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