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MELK-8a
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MELK-8a图片
CAS NO:1922153-17-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 432.56
Formula C25H32N6O
CAS No. 1922153-17-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:>10 mM
Water: <1 mg/mL
Ethanol: N/A
SMILES CodeCN(CC1)CCN1C2=CC=C(N3C=C(C4=CC=NC=C4OCC5CCNCC5)C=N3)C=C2
SynonymsMELK-8a; MELK 8a; MELK8a
实验参考方法
In Vitro

In vitro activity: MELK-8a is a novel and potent MELK inhibitor. MELK kinase has been implicated in playing an important role in tumorigenesis. MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. MELK inhibitors 8a recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. It was found that a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.


Kinase Assay: MELK-8a hydrochloride is a novel maternal embryonic leucine zipper kinase (MELK) inhibitor with an IC50 of 2 nM.


Cell Assay: MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. 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

In VivoSubcutaneous 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 (Tmax=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.
Animal modelC57BL/6 male mice
Formulation & Dosage10, 30 mg/kg; s.c.
References J Med Chem. 2016 May 26;59(10):4711-23.