Binimetinib (MEK162)

製品コードS7007 バッチS700704

化学情報

	Synonyms	ARRY-162,ARRY-438162	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₁₅BrF₂N₄O₃
	分子量	441.23	CAS No.	606143-89-9
Solubility (25°C)*	体外	DMSO	88 mg/mL warmed with 50ºC water bath (199.44 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3.
in vitro	ARRY-438162 (625 nM) inhibits in vitro osteoclast differentiation with IC50 of 39 nM. ARRY-438162 (10 μM) inhibits in vitro osteoclast resorption with IC50 of 625 nM. ARRY-438162 (2 μM) weakly affects osteoblast differentiation. ^[2] ARRY-438162 is a recently disclosed potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of11 nM. ^[3] MEK162 (1 μM) combined with MK-2206 (2 μM) completely reverses the resistance of RSK-expressing MCF7 cells. ^[4]
in vivo	ARRY-438162 (10 mg/kg, po, bid) reduces disease severity in a dose-related manner in rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models. ARRY-438162 (po, bid) inhibits increases in ankle diameter by 27% and 50% at 1 mg/kg and 3 mg/kg in the rat collagen-induced arthritis (CIA) model, while ibuprofen has 46% inhibition. ARRY-438162 (10 mg/kg, po, bid) significantly inhibits lesions (inflammation, cartilage damage, pannus formation and bone resorption) by 32% and 60% at 1 mg/kg and 3 mg/kg in the rat collagen-induced arthritis (CIA) model. ARRY-438162 inhibits AIA ankle diameter 11% and 34% at 3 mg/kg and 10 mg/kg in rat adjuvant-induced arthritis (AIA) models. ^[1] ARRY-438162 demonstrates dose-related inhibition of ankle swelling in rat adjuvant-induced arthritis (AIA) models, significant at 10 mg/kg and 30 mg/kg when compared to vehicle control. ARRY-438162 demonstrates dose-related inhibition of serum IL-6 concentration in rat adjuvant-induced arthritis (AIA) models, with complete inhibition at 10 mg/kg when compared to vehicle control. ARRY-438162 (30 mg/kg) demonstrates dose-related inhibition of relative spleen weights in rat adjuvant-induced arthritis (AIA) models. ARRY-438162 (30 mg/kg) significantly inhibits bone resorption and inflammation with delayed dosing when compared to vehicle in rat adjuvant-induced arthritis (AIA) models. ^[2] MEK162 (6 mg/kg, BID) combined with BEZ235 results in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. ^[4]

製品説明

Binimetinib (MEK162, ARRY-162, ARRY-438162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. Binimetinib induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and induces autophagy. Phase 3.

in vitro

ARRY-438162 (625 nM) inhibits in vitro osteoclast differentiation with IC50 of 39 nM. ARRY-438162 (10 μM) inhibits in vitro osteoclast resorption with IC50 of 625 nM. ARRY-438162 (2 μM) weakly affects osteoblast differentiation. ^[2]

ARRY-438162 is a recently disclosed potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of11 nM. ^[3]

MEK162 (1 μM) combined with MK-2206 (2 μM) completely reverses the resistance of RSK-expressing MCF7 cells. ^[4]

in vivo

ARRY-438162 (10 mg/kg, po, bid) reduces disease severity in a dose-related manner in rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models. ARRY-438162 (po, bid) inhibits increases in ankle diameter by 27% and 50% at 1 mg/kg and 3 mg/kg in the rat collagen-induced arthritis (CIA) model, while ibuprofen has 46% inhibition. ARRY-438162 (10 mg/kg, po, bid) significantly inhibits lesions (inflammation, cartilage damage, pannus formation and bone resorption) by 32% and 60% at 1 mg/kg and 3 mg/kg in the rat collagen-induced arthritis (CIA) model. ARRY-438162 inhibits AIA ankle diameter 11% and 34% at 3 mg/kg and 10 mg/kg in rat adjuvant-induced arthritis (AIA) models. ^[1]

ARRY-438162 demonstrates dose-related inhibition of ankle swelling in rat adjuvant-induced arthritis (AIA) models, significant at 10 mg/kg and 30 mg/kg when compared to vehicle control. ARRY-438162 demonstrates dose-related inhibition of serum IL-6 concentration in rat adjuvant-induced arthritis (AIA) models, with complete inhibition at 10 mg/kg when compared to vehicle control. ARRY-438162 (30 mg/kg) demonstrates dose-related inhibition of relative spleen weights in rat adjuvant-induced arthritis (AIA) models. ARRY-438162 (30 mg/kg) significantly inhibits bone resorption and inflammation with delayed dosing when compared to vehicle in rat adjuvant-induced arthritis (AIA) models. ^[2]

MEK162 (6 mg/kg, BID) combined with BEZ235 results in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. ^[4]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	KPCN cells
	濃度	10 nM
	反応時間
	実験の流れ	Cells were treated with indicated concentrations of drug.
動物実験	動物モデル	immunodeficient mice injected with MCF7-RSK4 cells.
	投薬量	6 mg/kg
	投与方法	oral

参考

+ 展开

カスタマーフィードバック

: Data from [Data independently produced by , , Clin Cancer Res, 2017, 23(20):6203-6214]

: Data from [Data independently produced by , , Eur J Cancer, 2018, 89:90-101]

: Data from [Data independently produced by , , Oncotarget, 2016, 7(50):82185-82199]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3]	PubMed: 38262581
Combined RAF and MEK Inhibition to Treat Activated Non-V600 BRAF-Altered Advanced Cancers [ Oncologist, 2024, 29(1):15-24]	PubMed: 37616543
N-acetylcysteine overcomes NF1 loss-driven resistance to PI3Kα inhibition in breast cancer [ Cell Rep Med, 2023, 4(4):101002]	PubMed: 37044095
Drug-repurposing screen on patient-derived organoids identifies therapy-induced vulnerability in KRAS-mutant colon cancer [ Cell Rep, 2023, 42(4):112324]	PubMed: 37000626
SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition [ NPJ Precis Oncol, 2023, 7(1):136]	PubMed: 38102334
High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer [ Mol Cancer Ther, 2023, 22(2):227-239]	PubMed: 36442478
Kinome profiling identifies MARK3 and STK10 as potential therapeutic targets in uveal melanoma [ J Biol Chem, 2023, S0021-9258(23)02446-8]	PubMed: 37923138
Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome [ Molecules, 2023, 28(2)692]	PubMed: 36677748
Neuronal differentiation drives the antitumor activity of mitogen-activated protein kinase kinase (MEK) inhibition in glioblastoma [ Neurooncol Adv, 2023, 5(1):vdad132]	PubMed: 38130900
Topical therapy for regression and melanoma prevention of congenital giant nevi [ Cell, 2022, S0092-8674(22)00472-X]	PubMed: 35561684

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。