Binimetinib

SKU: orb1305378

特色

描述

Binimetinib (ARRY-162) is an orally bioavailable, selective MEK1/2 inhibitor (IC50=12 nM). It exhibits antitumor activity and is used in research for unresectable or BRAF V600E/K mutant metastatic melanoma. Its application extends to in vitro signaling studies and in vivo xenograft models investigating MAPK pathway inhibition.

研究领域

Cell Biology, Pharmacology & Drug Discovery, Signal Transduction

图片与验证

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关键属性

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CAS 号	606143-89-9
MW	441.23
纯度	>98%
分子式	C₁₇H₁₅BrF₂N₄O₃
SMILES	Cn1cnc2c(F)c(Nc3ccc(Br)cc3F)c(cc12)C(=O)NOCCO
靶点	Kinase
溶解性	Soluble in DMSO (up to at least 25 mg/ml)

生物活性

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靶点 IC50	MEK:12 nM
体内	ARRY-438162 is an ATP non-competitive inhibitor for MEK1/2, capable of inhibiting intracellular pERK with an IC50 of 11 nM. When used in combination, MEK162 (1 μM) and MK-2206 (2 μM) can fully reverse the resistance of MCF7 cells expressing RSK. ARRY-438162 at 2 μM exhibits minimal impact on osteoblast differentiation. At a concentration of 10 μM, ARRY-438162 inhibits osteoclast resorption in vitro with an IC50 of 625 nM. Additionally, ARRY-438162 at 625 nM suppresses osteoclast differentiation in vitro with an IC50 of 39 nM.
体外	In models of collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) in rats, ARRY-438162 demonstrated significant anti-inflammatory effects. At doses of 1/3 mg/kg administered twice daily orally (p.o.), ARRY-438162 reduced ankle diameter swelling by 27%/50% in the CIA model, outperforming ibuprofen's 46% reduction. Higher doses of 3/10 mg/kg showed 11%/34% inhibition of ankle swelling in the AIA model. Moreover, in immunodeficient mice injected with MCF7-RSK4 cells, the combination of ARRY-438162 (6 mg/kg, twice daily) with BEZ235 significantly diminished tumor growth. In the AIA rat model, ARRY-438162 (10 mg/kg) completely suppressed serum IL-6 concentrations in a dose-dependent manner compared to controls. Similarly, in both CIA and AIA rat models, administration of ARRY-438162 (10 mg/kg, twice daily p.o.) dose-dependently ameliorated disease severity. The same dosing regimen significantly mitigated lesions (inflammation, cartilage damage, angiogenesis, and bone resorption) in the CIA model, with 1/3 mg/kg doses inhibiting these effects by 32% and 60%, respectively. Furthermore, in the AIA rat model, ARRY-438162 at 10/30 mg/kg doses significantly and dose-dependently reduced ankle swelling compared to control groups.
细胞研究	MEK162 is dissolved in DMSO and stored, and then diluted with appropriate medium before use. 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.

储存与操作

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储存	-20°C
有效期	12 months from date of receipt.
免责声明	For research use only

别名

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ARRY-162; MEK162

相似产品

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Binimetinib [orb1224490]
纯度：
>98% (HPLC)
CAS 号：
606143-89-9
MW:
441.23
分子式：
C₁₇H₁₅BrF₂N₄O₃
可选规格： 5 mg, 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, 500 mg, 1 g

质量保证

Explore bioreagents carefree to elevate your research. All our products are rigorously tested for performance. If a product does not perform as described on its datasheet, our scientific support team will provide expert troubleshooting, a prompt replacement, or a refund. For full details, please see our 条款与条件和选购指南.

化合物标识

PubChem CID

10288191 ↗

关键属性

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暂无计算属性。

实验方案信息

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纯度：	>98% (HPLC)
CAS 号：	606143-89-9
MW:	441.23
分子式：	C₁₇H₁₅BrF₂N₄O₃

Binimetinib

描述

研究领域

图片与验证

关键属性

生物活性

储存与操作

别名

相似产品

Binimetinib [orb1224490]

质量保证

化合物标识

关键属性

实验方案信息

可选规格