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    MELK-8a
    MELK-8a

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V2913
    CAS #: 1922153-17-0Purity ≥98%

    Description: MELK-8a is a novel, highly potent and selective MELK (Maternal Embryonic Leucine Zipper Kinase) 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.

    Reference:  2016 May 26;59(10):4711-23. 

    Related CAS #: 2096992-20-8 (HCl)


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    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


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    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  2016 May 26;59(10):4711-23.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

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