Binimetinib 是一种可口服的选择性MEK1/2抑制剂，抑制MEK的IC50为 12 nM。

Binimetinib (MEK162, ARRY-162, ARRY-438162) is an orally available inhibitor of MEK1/2 (IC50: 12 nM) in a cell-free assay.

在大鼠胶原诱导性关节炎模型中,ARRY-438162（1/3 mg/kg,2次/天,p.o.）抑制踝关节直径增加（27%/50%）,而布洛芬处理可抑制46%.在大鼠佐剂诱发性关节炎模型中,ARRY-438162（3/10 mg/kg）抑制AIA踝关节直径（11%/34%）.在注射MCF7-RSK4细胞的免疫缺陷小鼠,ARRY-438162（6 mg/kg,2次/天）与BEZ235联用可使肿瘤生长显著降低.在大鼠佐剂诱发性关节炎模型中,与对照组相比,ARRY-438162（10 mg/kg）剂量依赖地完全抑制血清中IL-6浓度.处理在大鼠胶原诱导性关节炎和佐剂诱发性关节炎模型中,ARRY-438162（10 mg/kg,2次/天p.o.）剂量依赖性地使疾病的严重程度降低.同样剂量处理大鼠胶原诱导性关节炎模型,可显著抑制病变（炎症,软骨损伤,血管翳形成,和骨重吸收）, ARRY-438162（1/3 mg/kg）处理则分别抑制32%和60%.处理在大鼠佐剂诱发性关节炎模型中,与对照组相比,ARRY-438162（10/30 mg/kg）剂量依赖性地显著抑制踝关节肿胀.

ARRY-438162是ATP非竞争性的MEK1/2抑制剂,可抑制细胞内pERK（IC50：11 nM）。MEK162（1 μM）与MK-2206（2 μM）联用可完全逆转表达RSK的MCF7细胞的抗性。ARRY-438162（2 μM）对成骨细胞分化的影响微弱。 ARRY-438162（10 μM）抑制体外破骨细胞再吸收（IC50：625 nM）。ARRY-438162（625 nM）抑制体外破骨细胞分化（IC50：39 nM）。

MEK162 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[2]. MCF7 cells infected as indicated are seeded in 12-well plates (2×104). After 24 hours, cells are treated with BEZ235 (100 or 200 nM), BKM120 (0.75 or 1 μM), GDC-0941 (1 μM), or MK2206 (2 μM) alone or in combination with MEK162 (1 μM), BI-D1870 (10 μM), or AZD6244 (1 μM), as indicated in text. Cell numbers are quantified by fixing cells with 4% glutaraldehyde or methanol, washing the cells twice in Water, and staining the cells with 0.1% crystal violet. The dye is subsequently extracted with 10% acetic acid, and its absorbance is determined (570 nm). Growth curves are performed in triplicate. Viability assays with CellTiter-Glo are performed by plating 2,000 cells in 96-well plates, adding the drug at 24 hours, and assaying 4 to 5 days after drug addition. Cell-cycle and hypodiploid apoptotic cells are quantified by flow cytometry. Briefly, cells are washed with PBS, fixed in cold 70% ethanol, and then stained with propidium iodide while being treated with RNase. Quantitative analysis of sub-G1 cells is carried out in a FACScalibur cytometer using Cell Quest software[2].

606143-89-9

C17H15BrF2N4O3

441.233

ARRY-438162;MEK162;ARRY-162

Ethanol:<1 mgml
H2O:<1 mgml
DMSO:82 mg/mL (185.8 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years