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 (Ki=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。
生物活性 | Merestinib dihydrochloride (LY2801653 dihydrochloride) is a potent, orally bioavailablec-Metinhibitor (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 IC50value (n=6 determinations) of Merestinib for inhibition of MET auto-phosphorylation in HGF-stimulated H460 cells is 35.2±6.9 nM and the IC50for 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 IC50ranging 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].
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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-1and t1/2of 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].
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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 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时,请在 6 个月内使用,-20℃ 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-CDin 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 μL20% 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。 *以上所有助溶剂都可在本网站选购。
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