MELK8A HYDROCHLORIDE

中文名称:

MELK8A HYDROCHLORIDE

中文同义词:

母体胚胎亮氨酸拉链激酶(MELK)抑制剂(MELK-8A HYDROCHLORIDE)

英文名称:

MELK-8a (hydrochloride)

英文同义词:

MELK-8a (hydrochloride);NVP-MELK8a hydrochloride

CAS号:

2096992-20-8

分子式:

C??H??ClN?O

分子量:

0

EINECS号:

相关类别:

细胞生物学试剂

Mol文件:

Mol File

生物活性

MELK-8a hydrochloride是一种新颖的母体胚胎亮氨酸拉链激酶（MELK）抑制剂，其IC50值为2 nM。

靶点

IC50: 2 nM (MELK)

体外研究

MELK-8a remains very potent (IC 50 =140 nM) when the ATP concentration in the biochemical assay is shifted from 20 μM to 2 mM. Its potency is well tracked between full-length MELK versus catalytic domain construct (5 nM versus 2 nM). It only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1 μM demonstrating great selectivity. The compound is at least 90-fold more selective in targeting MELK in all cases. MELK-8a is fairly soluble (0.22 g/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 IC 50 of approximately 0.06 and 1.2 μM, respectively.

体内研究

Subcutaneous administration of MELK-8a at 30 mg/kg in C57BL/6 mice results in good plasma exposure. The compound adsorption into the systemic circulation is rapid (T max =0.4 h) and peak plasma concentration reaches 6.6 μM. An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120 mg/kg and all clearance mechanisms can be saturated at 240 mg/kg. However, when administered orally at 10 mg/kg in C57BL/6 male mice, it shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance.