Merestinib dihydrochloride是一种有

Merestinib dihydrochloride  (Synonyms: LY2801653 dihydrochloride)

Merestinib dihydrochloride (LY2801653 dihydrochloride) 是一种有效的口服生物可利用的具有抗肿瘤活性的 c-Met 抑制剂 (K_i=2 nM)。Merestinib dihydrochloride 对 MST1R (IC₅₀=11 nM)、FLT3 (IC₅₀=7 nM)、AXL (IC₅₀=2 nM)、MERTK (IC₅₀=10 nM)、TEK (IC₅₀=63 nM)、ROS1、DDR1/2 (IC₅₀=0.1/7 nM) 和 MKNK1/2 (IC₅₀=7 nM) 也有较强的活性。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。

生物活性    
Merestinib dihydrochloride (LY2801653 dihydrochloride) is a potent, orally bioavailable c-Met inhibitor (Ki=2 nM) with anti-tumor activities. Merestinib dihydrochloride also has potent activity against MST1R (IC50=11 nM), FLT3 (IC50=7 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TEK (IC50=63 nM), ROS1, DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM)[1][2].

IC50 & Target    
Ki: 2 nM (c-Met)[1]
IC50: 11 nM (MST1R), 7 nM (FLT3), 2 nM (AXL), 10 nM (MERTK), 63 nM (TEK), 0.1/7 nM (DDR1/2), 7 nM (MKNK1/2)[1]

体外研究(In Vitro)    
Merestinib (LY2801653) also inhibits MST1R (IC50=11 nM), AXL (IC50=2 nM), MERTK (IC50=10 nM), TYRO3 (IC50=28 nM), ROS1, PDGFRA (IC50=41 nM), FLT3 (IC50=7 nM), TEK (IC50=63 nM), DDR1/2 (IC50=0.1/7 nM) and MKNK1/2 (IC50=7 nM)[1].
Merestinib demonstrates effects on MET pathway-dependent cell scattering and cell proliferation. The mean IC50 value (n=6 determinations) of Merestinib for inhibition of MET auto-phosphorylation in HGF-stimulated H460 cells is 35.2±6.9 nM and the IC50 for MET auto-phosphorylation in S114 cells is 59.2 nM. Transfection with the MET variants confers growth-factor independence and treatment with Merestinib inhibits growth of these MET variant clones with an IC50 ranging from 3-fold more potent (V1092I) to approximately 6-fold less potent (L1195V) compare with the growth inhibition of cells with the MET wild-type sequence[1].
Merestinib (2, 5, and 10 μM) reduces the number of viable TFK-1 and SZ-1 cells in a dose and time dependent manner, and significant inhibits wound healing for TFK-1 and SZ-1 cell lines. Merestinib inhibits cell invasion in TFK-1 and SZ-1 cells in a concentration dependent manner[2].

体内研究(In Vivo)    
Merestinib (LY2801653) demonstrates anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects. Merestinib (LY2801653) is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a pharmacodynamic residence time (Koff) of 0.00132 min-1 and t1/2 of 525 min. Merestinib (LY2801653) treatment inhibits MET phosphorylation with a composite TED50 (50 % target inhibition dose) of 1.2 mg/kg and a composite TED90 (90 % target inhibition dose) of 7.4 mg/kg[1]. Merestinib (LY2801653) (20 mg/kg) reduces TFK-1 tumor growth significantly relative to vehicle control. Merestinib (LY2801653) inhibits the growth of intra- and extrahepatic CCC xenograft tumors[2].


分子量    
625.45

性状    
Solid

Formula    
C30H24Cl2F2N6O3

CAS 号    
1206801-37-7

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据    
In Vitro: 
DMSO : ≥ 100 mg/mL (159.88 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    1.5988 mL    7.9942 mL    15.9885 mL
5 mM    0.3198 mL    1.5988 mL    3.1977 mL
10 mM    0.1599 mL    0.7994 mL    1.5988 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 (sealed storage, away from moisture)。-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: ≥ 2.5 mg/mL (4.00 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

以 1 mL 工作液为例，取 100 μL 25.0 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。

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (4.00 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

以 1 mL 工作液为例，取 100 μL 25.0 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。

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.5 mg/mL (4.00 mM); Clear solution

此方案可获得 ≥ 2.5 mg/mL (4.00 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

 

参考文献	[1]. Yan SB, et al. LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models. Invest New Drugs. 2013 Aug;31(4):833-44. [Content Brief] [2]. Barat S, et al. Targeting c-MET by LY2801653 for treatment of cholangiocarcinoma. Mol Carcinog. 2016 Jan 12.  [Content Brief]