Avutometinib (Synonyms: Ro 5126766; CH5126766)

目录号: HY-18652 纯度: 99.02%: Data Sheet SDS COA 产品使用指南
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技术支持

Avutometinib (Ro 5126766) 是一种有效的双重 MEK/RAF 抑制剂，抑制 BRAF^V600E，CRAF, MEK，和 BRAF，IC₅₀ 分别为 8.2 nM, 56 nM, 160 nM 和 190 nM。

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Avutometinib Chemical Structure

CAS No. : 946128-88-7

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规格	价格	是否有货
10 mM * 1 mL in DMSO	￥1660	In-stock
1 mg	￥727	In-stock
5 mg	￥1600	In-stock
10 mg	￥2600	In-stock
25 mg	￥4607	In-stock
50 mg	现货	询价
100 mg	现货	询价
500 mg	现货	询价
1 g		询价
5 g		询价

or 大包装询价

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Customer Review

Other Forms of Avutometinib:

Avutometinib potassium 询价

MCE 顾客使用本产品发表的 3 篇科研文献

Avutometinib 相关产品

•相关化合物库:

•同靶点产品:

•同靶点蛋白产品:

查看 MEK 亚型特异性产品:

查看所有亚型

MEK1 MEK2 MEK5 MEK MAP2K4/MEK4

查看 Raf 亚型特异性产品:

查看所有亚型

B-Raf C-Raf Raf

生物活性
实验参考方法
纯度 & 产品资料
参考文献

生物活性

Avutometinib (Ro 5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAF^V600E, CRAF, MEK, and BRAF (IC₅₀: 8.2, 56, 160 nM, and 190 nM, respectively).

IC₅₀ & Target^[1]

MEK

160 nM (IC₅₀)

BRaf^V600E

8.2 nM (IC₅₀)

Braf

190 nM (IC₅₀)

CRAF

56 nM (IC₅₀)

细胞效力
(Cellular Effect)

Cell Line	Type	Value	Description	References
A549	IC₅₀	1.24 μM Compound: 3; RO5126766	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
C32	ED₅₀	0.09 mg/kg Compound: 1, CH5126766/RO5126766	Antitumor activity against human C32 cells xenografted in po dosed BALB-nu/nu mouse assessed as tumor growth inhibition administered qd for 11 days Antitumor activity against human C32 cells xenografted in po dosed BALB-nu/nu mouse assessed as tumor growth inhibition administered qd for 11 days	[PMID: 24900832]
HCT-116	IC₅₀	0.053 μM Compound: 3; RO5126766	Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
HCT-116	IC₅₀	277 nM Compound: 1; VS6766	Antiproliferative activity against human HCT-116 cells harboring NRAS G13D mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human HCT-116 cells harboring NRAS G13D mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
HCT-116	IC₅₀	40 nM Compound: 1, CH5126766/RO5126766	Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis Inhibition of human HCT116 cell growth after 96 hrs by counting kit-8 analysis	[PMID: 24900832]
HL-60	IC₅₀	0.006 μM Compound: 3; RO5126766	Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
L02	IC₅₀	17.27 μM Compound: 3; RO5126766	Cytotoxicity against human HL7702 cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay Cytotoxicity against human HL7702 cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MDA-MB-231	IC₅₀	0.17 μM Compound: 3; RO5126766	Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MIA PaCa-2	IC₅₀	40 nM Compound: 1; VS6766	Antiproliferative activity against human MIA PaCa-2 cells harboring NRAS G12C mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human MIA PaCa-2 cells harboring NRAS G12C mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SK-MEL-2	IC₅₀	28 nM Compound: 1; VS6766	Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SK-MEL-2 cells harboring NRAS Q61R mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SK-MEL-28	IC₅₀	65 nM Compound: 1; VS6766	Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SK-MEL-28 cells harboring BRAF V600E mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
SW480	IC₅₀	46 nM Compound: 1; VS6766	Antiproliferative activity against human SW480 cells harboring NRAS G12V mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay Antiproliferative activity against human SW480 cells harboring NRAS G12V mutant assessed as cell growth inhibition measured after 72 hrs by WST-8 assay	[PMID: 35849914]
Vero	IC₅₀	> 50 μM Compound: 3; RO5126766	Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]

体外研究
(In Vitro)

Avutometinib (Ro 5126766) 是一种变构抑制剂，可直接结合 MEK 并通过形成稳定的 RAF-MEK 复合物，阻止 RAF 对 MEK 的磷酸化。Avutometinib 能双重抑制 RAF 对 MEK 的磷酸化作用以及 MEK 对 ERK 的激活作用。在无细胞 MEK 和 RAF 激酶实验中，Avutometinib 可有效抑制 MEK1 对 ERK2 的激活（IC₅₀=160 nM），并抑制BRAF（IC₅₀=190 nM）、BRAF^V600E（IC₅₀=8.2 nM）和CRAF（IC₅₀=56 nM）对 MEK1 蛋白的磷酸化。在包括 KRAS/HRAS 及 BRAF 突变细胞系与野生型细胞在内的多组人类肿瘤细胞系中，Avutometinib 均能有效抑制 MEK 和 ERK 的磷酸化^[1]。
Avutometinib 与 XU 62-320 联用比单药治疗能更显著地以剂量依赖性方式抑制KRAS和BRAF突变的人乳腺癌 MDA-MB-231 细胞生长。40 nM Avutometinib 与 0.3 μM XU 62-320 联用对细胞集落形成的抑制作用也得到证实^[2]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

在KRAS突变异种移植模型中，Avutometinib (Ro 5126766) 相比另一种变构 MEK 抑制剂 PD0325901 能更有效地抑制肿瘤生长并诱导肿瘤消退。来自多组人类肿瘤小鼠异种移植模型的临床前数据显示，Avutometinib 的 ED₅₀为 0.03-0.23 mg/kg，ED₉₀ 为 0.15-1.56 mg/kg，这些有效剂量对应的目标浓度分别为 17-133 ng/mL 和 87-901 ng/mL^[1]。
Avutometinib 和 PD0325901 分别以 HCT116 模型中的最大耐受剂量 (1.5 mg/kg 和 25 mg/kg) 给药。首次给药 4 小时后，两种剂量在受试小鼠肿瘤中均能相似程度地抑制 pERK 和 ERK 信号输出。在 HCT116 模型中，Avutometinib 和 PD0325901的 ED₅₀ 分别为 0.056 mg/kg 和 0.80 mg/kg，表明本实验所用剂量分别是其 ED₅₀ 的 26.8 倍和 31.3 倍。每日口服任一种药物均能显著诱导肿瘤消退，但 Avutometinib 治疗组小鼠在整个28 天治疗期内均维持肿瘤生长抑制效果，而 PD0325901 治疗组在给药 10 天后出现耐药^[3]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

471.46

Formula

C₂₁H₁₈FN₅O₅S

CAS 号

946128-88-7

性状

固体

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

溶解性数据

细胞实验：

DMSO 中的溶解度 : 100 mg/mL (212.11 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.1211 mL	10.6054 mL	21.2107 mL
5 mM	0.4242 mL	2.1211 mL	4.2421 mL
10 mM	0.2121 mL	1.0605 mL	2.1211 mL

查看完整储备液配制表

* 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, 6 months; -20°C, 1 month。-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。

摩尔计算器
稀释计算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

浓度 _(start)

体积 _(start)

浓度 _(final)

体积 _(final)

动物实验：

请根据您的实验动物和给药方式选择适当的溶解方案。

以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：
——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

方案一

请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (10.61 mM); 澄清溶液

此方案可获得 ≥ 5 mg/mL（饱和度未知）的澄清溶液。
以 1 mL 工作液为例，取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水定容至 1 mL。
生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。
方案二

请依序添加每种溶剂： 10% DMSO 90% Corn Oil
Solubility: ≥ 5 mg/mL (10.61 mM); 澄清溶液

此方案可获得 ≥ 5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。
以 1 mL 工作液为例，取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
方案三

请依序添加每种溶剂： 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.41 mM); 澄清溶液

此方案可获得 ≥ 2.08 mg/mL（饱和度未知）的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。

动物溶解方案计算器

请输入动物实验的基本信息：

给药剂量

mg/kg

动物的平均体重

每只动物的给药体积

μL

动物数量

只

由于实验过程有损耗，建议您多配一只动物的量

请输入您的动物体内配方组成：

DMSO +

Tween-80 +

Saline

如果您的动物是免疫缺陷鼠或者体弱鼠，建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。

方案所需 助溶剂 包括：DMSO，，均可在 MCE 网站选购。，Tween 80，均可在 MCE 网站选购。

计算结果

工作液所需浓度 : mg/mL

储备液配制方法 : mg 药物溶于 μL DMSO（母液浓度为 mg/mL）。

您所需的储备液浓度超过该产品的实测溶解度，以下方案仅供参考，如有需要，请与 MCE 中国技术支持联系。

动物实验体内工作液的配制方法 : 取 μL DMSO 储备液，加入 μL 。 μL ，混合均匀至澄清，再加 μL Tween 80，混合均匀至澄清，再加 μL 生理盐水。

连续给药周期超过半月以上，请谨慎选择该方案。

请确保第一步储备液溶解至澄清状态，从左到右依次添加助溶剂。您可采用超声加热（超声清洗仪，建议频次 20-40 kHz），涡旋吹打等方式辅助溶解。

纯度 & 产品资料

纯度: 99.02%

选择批次：

Data Sheet (661 KB) SDS (393 KB)

COA (284 KB) LCMS (92 KB)

产品使用指南 (1538 KB)

参考文献

[1]. Martinez-Garcia M, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012 Sep 1;18(17):4806-19. [Content Brief]

[2]. Iizuka-Ohashi M, et al. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. Oncotarget. 2018 Apr 13;9(28):19597-19612. [Content Brief]

[3]. Ishii N, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res. 2013 Jul 1;73(13):4050-4060. [Content Brief]

Cell Assay ^[2]	The number of viable cells is assessed with a Cell Counting Kit-8 assay. Human breast cancer MDA-MB-231 cells, human melanoma SK-MEL-28 cells, and human non-small cell lung cancer A549 cells are seeded at a density of 2,000 cells per well in 96-well plates and incubated for 24 h, and then treated with Ro 5126766 (10, 20, 40, and 80 nM) for 72 h. After a further 4 h incubation with the kit reagent, the absorbance at 450 nm of the samples is measured using a multi-plate reader^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[3]	Mice^[3] Female BALB-nu/nu mice (CAnN.Cg-Foxn1nu/CrlCrlj nu/nu) are given access to standard mouse chow and water ad libitum. A total of 5×10⁶ (HCT116) or 1×10⁷ (Calu-6 and COLO205) tumor cells per mouse are injected subcutaneously into the right flank of the 7- to 9-week-old mice. When tumor volume reaches to 200 mm³ (day 0), the mice are randomized and vehicle [5% DMSO and 10% 2-hydroxypropyl-β-cyclodextrin (HPCD) solution in distilled water], Avutometinib (1.5 mg/kg or 2.0 mg/kg) or PD0325901 (25 mg/kg) is administered orally once a day. Drugs are administrated at the maximum tolerated dose (MTD). Tumor growth inhibition (TGI) is calculated. The value of the 50% effective dose (ED₅₀) for each compound is calculated^[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献	[1]. Martinez-Garcia M, et al. First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK/RAF inhibitor in patients with solid tumors. Clin Cancer Res. 2012 Sep 1;18(17):4806-19. [Content Brief] [2]. Iizuka-Ohashi M, et al. Blockage of the mevalonate pathway overcomes the apoptotic resistance to MEK inhibitors with suppressing the activation of Akt in cancer cells. Oncotarget. 2018 Apr 13;9(28):19597-19612. [Content Brief] [3]. Ishii N, et al. Enhanced inhibition of ERK signaling by a novel allosteric MEK inhibitor, CH5126766, that suppresses feedback reactivation of RAF activity. Cancer Res. 2013 Jul 1;73(13):4050-4060. [Content Brief]

Avutometinib 相关分类

完整储备液配制表

可选溶剂	浓度溶剂体积质量	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.1211 mL	10.6054 mL	21.2107 mL	53.0268 mL
	5 mM	0.4242 mL	2.1211 mL	4.2421 mL	10.6054 mL
	10 mM	0.2121 mL	1.0605 mL	2.1211 mL	5.3027 mL
	15 mM	0.1414 mL	0.7070 mL	1.4140 mL	3.5351 mL
	20 mM	0.1061 mL	0.5303 mL	1.0605 mL	2.6513 mL
	25 mM	0.0848 mL	0.4242 mL	0.8484 mL	2.1211 mL
	30 mM	0.0707 mL	0.3535 mL	0.7070 mL	1.7676 mL
	40 mM	0.0530 mL	0.2651 mL	0.5303 mL	1.3257 mL
	50 mM	0.0424 mL	0.2121 mL	0.4242 mL	1.0605 mL
	60 mM	0.0354 mL	0.1768 mL	0.3535 mL	0.8838 mL
	80 mM	0.0265 mL	0.1326 mL	0.2651 mL	0.6628 mL
	100 mM	0.0212 mL	0.1061 mL	0.2121 mL	0.5303 mL

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Avutometinib946128-88-7Ro 5126766 CH5126766Ro5126766Ro-5126766CH5126766CH 5126766CH-5126766MEKRafMitogen-activated protein kinase kinaseMAPKKMAP2KRaf kinasesInhibitorinhibitorinhibit

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Avutometinib (Synonyms: Ro 5126766; CH5126766)

Customer Review

Other Forms of Avutometinib:

MCE 顾客使用本产品发表的 3 篇科研文献

Avutometinib 相关产品

•相关化合物库:

•同靶点产品:

•同靶点蛋白产品:

查看 MEK 亚型特异性产品:

查看 Raf 亚型特异性产品:

生物活性

实验参考方法

纯度 & 产品资料

参考文献

摩尔计算器

稀释计算器

Avutometinib 相关分类

完整储备液配制表

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Avutometinib (Synonyms: Ro 5126766; CH5126766)

Customer Review

Other Forms of Avutometinib:

Avutometinib 相关抗体

MCE 顾客使用本产品发表的 3 篇科研文献

Avutometinib 相关产品

•相关化合物库:

•同靶点产品:

•同靶点蛋白产品:

查看 MEK 亚型特异性产品:

查看 Raf 亚型特异性产品:

生物活性

实验参考方法

纯度 & 产品资料

参考文献

Avutometinib 相关抗体:

摩尔计算器

稀释计算器

Avutometinib 相关分类

完整储备液配制表

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