| 中文名称: | MELK-8a hydrochloride | ||||
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| 英文名称: | MELK-8a hydrochloride | ||||
| 别名: | MELK-8a HCl 1-methyl-4-(4-(4-(3-(piperidin-4-ylmethoxy)pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)piperazine hydrochloride | ||||
| CAS No: | 2096992-20-8 | 分子式: | C25H33ClN6O | 分子量: | 469.02 |
| CAS No: | 2096992-20-8 | ||||
| 分子式: | C25H33ClN6O | ||||
| 分子量: | 469.02 | ||||
基本信息
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产品编号： |
M11673 |
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产品名称： |
MELK-8a hydrochloride |
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CAS: |
2096992-20-8 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
6个月 |
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分子量： |
469.02 |
-20℃ |
1个月 |
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化学名： |
1-methyl-4-(4-(4-(3-(piperidin-4-ylmethoxy)pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)piperazine hydrochloride |
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Solubility (25°C)： |
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体外:
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DMSO |
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Ethanol |
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Water |
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体内(现配现用): |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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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。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
2.1321mL |
10.6605mL |
21.3211mL |
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5mM |
0.4264mL |
2.1321mL |
4.2642mL |
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10mM |
0.2132mL |
1.0661mL |
2.1321mL |
生物活性
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产品描述 |
一种新颖的母体胚胎亮氨酸拉链激酶（MELK）抑制剂，其IC50值为2nM。 |
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靶点 |
IC50:2nM (MELK) |
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体外研究 |
MELK-8a remains very potent (IC50=140nM) when the ATP concentration in the biochemical assay is shifted from 20μM to 2mM.Its potency is well tracked between full-length MELK versus catalytic domain construct (5nM versus 2nM).It only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1μM demonstrating great selectivity.The compound is at least 90-fold more selective in targeting MELK in all cases.MELK-8a is fairly soluble (0.22g/L at pH 6.8) and shows a good permeability in the Caco-2 assay.MELK-8a inhibits the growth of MDA-MB-468 cells and MCF-7 cells with an IC50 of approximately 0.06 and 1.2μM,respectively. |
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体内研究 |
Subcutaneous administration of MELK-8a at 30mg/kg in C57BL/6 mice results in good plasma exposure.The compound adsorption into the systemic circulation is rapid (Tmax=0.4h) and peak plasma concentration reaches 6.6μM.An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120mg/kg and all clearance mechanisms can be saturated at 240mg/kg.However,when administered orally at 10mg/kg in C57BL/6 male mice,it shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance. |
推荐实验方法(仅供参考)
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细胞实验: |
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MDA-MB-468 and MCF7 cells are seeded in growth medium into 96-well plates at 1000 and 4000 cells/well,respectively.Sixteen hours after plating,MELK-8a are added and incubated for 7 days.For each well,ATPLite reagent is added and incubated.Luminescence is measured on an multilabel plate reader. |
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动物实验: |
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Mice:For pharmacokinetic studies,the intravenous and oral dose is prepared in a solution containing 5% ethanol,100% PG,5% CremophorEL,and 80% PBS.The subcutaneous dose is formulated in 10% PG and 25% (20%,v/v) Solutol.Plasma samples are collected at specified time points and stored frozen (−20℃) until MELK-8a analysis.An LC−MS/MS method is used to quantitate MELK-8a drug levels in plasma. |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
