MK-8033|cas:1001917-37-8|西域试剂

MK-8033,98.06%

产品编号：Bellancom-13299| CAS NO：1001917-37-8| 分子式：C₂₅H₂₁N₅O₃S| 分子量：471.53

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-13299	￥2386.00	杭州北京（现货）
Bellancom-13299	￥3580.00	杭州北京（现货）
Bellancom-13299	￥5800.00	杭州北京（现货）
Bellancom-13299	￥13800.00	杭州北京（现货）

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MK-8033

产品介绍

MK-8033 是一种具有口服活性的 ATP 竞争性 c-Met/Ron 双重抑制剂 (IC₅₀s: 1 nM (c-Met)，7 nM (Ron))，优先结合活化的激酶构象 (activated kinase conformation)。MK-8033 可用于癌症的研究，例如乳腺癌，膀胱癌、非小细胞肺癌 (NSCLC)。

生物活性

MK-8033 is an orally active ATP competitive c-Met/Ron dual inhibitor (IC₅₀s: 1 nM (c-Met),7 nM (Ron)), with preferential binding to the activated kinase conformation. MK-8033 can be used in the research of cancers, such as breast and bladder cancers, non-small cell lung cancers (NSCLCs).

体外研究

MK-8033 (Compound 11r, 10 μM) displayed 31% inhibition of CYP3A4 (cytochrome P450 3A4).
MK-8033 (1 μM, 2 h) inhibits phosphorylation of Y1349 of c-Met (IC₅₀: 0.03 μM) in the c-Met dependent gastric cancer cell line GTL-16.
MK-8033 (1-10 μM, 72 h) inhibits GTL-16 cell proliferation (IC₅₀: 0.58 μM).
MK-8033 binds more tightly to phosphorylated c-Met (K_d: 3.2 nM) than to its unphosphorylated counterpart (K_d: 10.4 nM), and inhibits oncogenic c-Met activation loop mutants with IC₅₀s ranging from 0.6 to 1 nM.
MK-8033 (0.1-10 μM, 2 h) reduces the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells.
MK-8033 (1 μM, 1 h) sensitizes EBC-1 and H1993 cells (high c-Met-expressing) to radiation.
MK-8033 (10 μM, 6 h) enhances γ-H2Ax levels in A549 cells compared to double irradiation and decreases in DNA repair.
MK-8033 (2 μM, 72 h) results in reduced cell proliferation, but modest induction of apoptosis in G-alpha protein mutant UM (uveal melanoma) cells.

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

Western Blot Analysis

Cell Line:	EBC-1, H1993 cells, A549 and H460 cells
Concentration:	0.1, 1, 10 μM
Incubation Time:	2 h
Result:	Reduced the phosphorylation of c-Met, ERK, and Akt in EBC-1 and H1993 cells in a dose-dependent manner.

体内研究
(In Vivo)

MK-8033 (Compound 11r, oral administration, 3-100 mg/kg, twice daily for 21 days) inhibits tumor growth in GTL-16 c-Met amplified gastric tumor xenografts.
MK-8033 exhibits moderate clearance (t_1/2: 0.8 h for rats, 3.1 h for dog) and favorable bioavailability (35% for rats, 33% for dog).

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

Animal Model:	Human GTL-16 c-Met amplified gastric tumor xenografts
Dosage:	3, 10, 30, and 100 mg/kg
Administration:	Oral administration, twice daily for 21 days
Result:	Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively. Inhibited c-Met (Y1349) phosphorylation.

体内研究

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

Animal Model:	Human GTL-16 c-Met amplified gastric tumor xenografts
Dosage:	3, 10, 30, and 100 mg/kg
Administration:	Oral administration, twice daily for 21 days
Result:	Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively. Inhibited c-Met (Y1349) phosphorylation.

体内研究

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

Animal Model:	Human GTL-16 c-Met amplified gastric tumor xenografts
Dosage:	3, 10, 30, and 100 mg/kg
Administration:	Oral administration, twice daily for 21 days
Result:	Resulted in 22, 18, 57, and 86% tumor growth inhibition at 3, 10, 30, and 100 mg/kg, respectively. Inhibited c-Met (Y1349) phosphorylation.

性状

Solid

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