中文名称: MELK-8a hydrochloride
英文名称: MELK-8a hydrochloride
CAS No: 2096992-20-8
分子式: C25H33ClN6O
分子量: 469.02
M11673 MELK-8a hydrochloride ≥98% (psaitong)
包装规格:
1mg 5mg 10mg 50mg 100mg in glass bottle
溶解性:
溶于水(≥100mg/mL)
产品描述:

基本信息

产品编号:

M11673 

产品名称:

MELK-8a hydrochloride

CAS:

2096992-20-8

 

储存条件

粉末

-20℃

四年

 

 

分子式:

C25H33ClN6O

溶于液体

-80℃

6个月

分子量:

469.02

-20℃

1个月

化学名: 

1-methyl-4-(4-(4-(3-(piperidin-4-ylmethoxy)pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)piperazine hydrochloride

Solubility (25°C):

 

体外:

 

DMSO

 

Ethanol

 

Water

 

体内(现配现用):

 

1mg/ml表示微溶或不溶。

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。

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。

 

制备储备液

 

浓度

 

溶液体积

质量

 

1mg

 

5mg

 

10mg

1mM

2.1321mL

10.6605mL

21.3211mL

5mM

0.4264mL

2.1321mL

4.2642mL

10mM

0.2132mL

1.0661mL

2.1321mL

 

生物活性

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。

靶点

IC50:2nM (MELK)

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.

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)

细胞实验:

 

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.

 

动物实验:

 

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.

保存条件:
-20℃
UN码:
HazardClass:
危害声明:
安全说明:
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参考文献 & 客户发表文献

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摩尔浓度计算公式

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    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
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    C8=C7/X C8: LOG(C8):