MK-8033

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

MK-8033  纯度: 95.02%

MK-8033 是ATP竞争性c-Met/Ron双重抑制剂,对野生型c-Met的IC50为1 nM,对c-Met N1100Y的IC50为2.0 nM。

MK-8033

MK-8033 Chemical Structure

CAS No. : 1001917-37-8

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥3714 In-stock
2 mg ¥2386 In-stock
5 mg ¥3580 In-stock
10 mg ¥5800 In-stock
50 mg ¥13800 In-stock
100 mg   询价  
200 mg   询价  

* Please select Quantity before adding items.

MK-8033 相关产品

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生物活性

MK-8033 is a novel and specific dual ATP competitive c-Met/Ron inhibitor (IC50=1 nM Wt c-Met) under investigation as a treatment for cancer. IC50 Value: 1 nM (Wt c-Met); 2.0 nM (c-Met N1100Y) [1] Target: c-Met/Ron in vitro: MK-8033 binds 3-fold more tightly to phosphorylated c-Met kinase domain (Kd= 3.2 nM) than to its unphosphorylated counterpart (Kd = 10.4 nM). Signigicantly, MK-8033 potently inhibits kinase activity of three oncogenic c-Met activation loop mutants, Y1230C, Y1230H, and Y1235D (IC50s ranging from 0.6 to 1 nM at 50 uM ATP) in addition to other c-Met activating mutants N1100Y and M1250T. MK-8033 potently inhibited GTL-16 proliferation with an IC50 of 582 ± 30 nM. By contrast the HCT116 cell line, which does not harbor basal c-Met activation, was not inhibited by MK-8033 (IC50 > 10000 nM) [1]. MK-8033 radiosensitized the high-c-Met-expressing EBC-1 and H1993 cells but not the low-c-Met-expressing cell lines A549 and H460. However, irradiation of A549 and H460 cells increased the expression of c-Met protein at 30 minutes after the irradiation. Subsequent targeting of this up-regulated c-Met by using MK-8033 followed by a second radiation dose reduced the clonogenic survival of both A549 and H460 cells. MK-8033reduced the levels of radiation-induced phosphorylated (activated) c-Met in A549 cells [2]. in vivo: MK-8033 was orally dosed in GTL-16 tumor xenograft bearing mice. Mice were euthanized 1 h after dosing and tested for p-Met (Y1349) in tumors and MK-8033 concentrations in plasma. At 100 mg/kg,essentially complete inhibition of p-Met (Y1349) was achieved. An in vivo IC50 of 1.3 uM was deduced from the relationship between plasma MK-8033 level and Met pY1349. Treatment with escalating dosed of MK-8033 for 21 days lead to antitumor efficacies in a dose-dependent manner. Dosing at 3, 10, 30, and 100 mg/kg resulted in 22, 18, 57, and 86% tumor growth inhibition, respectively, relative to tumor from vehicle-treated mice. signatures.

Clinical Trial

分子量

471.53

Formula

C25H21N5O3S

CAS 号

1001917-37-8

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
In Vitro: 

DMSO : ≥ 46 mg/mL (97.55 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.1208 mL 10.6038 mL 21.2076 mL
5 mM 0.4242 mL 2.1208 mL 4.2415 mL
10 mM 0.2121 mL 1.0604 mL 2.1208 mL

*

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。

In Vivo:

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

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1 mg/mL (2.12 mM); Clear solution

    此方案可获得 ≥ 1 mg/mL (2.12 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 1 mg/mL (2.12 mM); Clear solution

    此方案可获得 ≥ 1 mg/mL (2.12 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 10.0 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。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Northrup AB, et al, Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): A Specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met. J Med Chem. 2013 Mar 28;56(6):2294-310.

    [2]. Bhardwaj V, et al. C-Met inhibitor MK-8003 radiosensitizes c-Met-expressing non-small-cell lung cancer cells with radiation-induced c-Met-expression. J Thorac Oncol. 2012 Aug;7(8):1211-7.

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