NVP-MELK8a hydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

NVP-MELK8a 盐酸盐 (MELK8a 盐酸盐) 是一种新型有效的选择性 MELK 抑制剂，IC50 为 2 nM。

NVP-MELK8a hydrochloride (MELK8a hydrochloride)?is a novel potent, and selective MELK inhibitor with IC50 of 2 nM; exhibits high selectivity with only 7 off-target kinases inhibited >85% against 456 kinases at 1 uM, Flt3 (IC50=0.18 uM), Haspin (IC50=0.19 uM), PDGFRα (IC50=0.42 uM); exhibits growth inhibition of MDA-MD-468 cells with IC50 of 0.11 uM, and increases cells harboring 4N DNA content.

MELK-8a remains very potent (IC50=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 IC50 of approximately 0.06 and 1.2 μM, respectively.

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 (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.

MELK8a hydrochloride

PI3K/Akt/mTOR signaling

MELK

MELK

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2096992-20-8

469.02212

C25H33ClN6O

>98% (HPLC)

DMSO: 8.6 mg/mL (Need ultrasonic and warming)

CN1CCN(CC1)C2=CC=C(C=C2)N3C=C(C=N3)C4=C(C=NC=C4)OCC5CCNCC5.Cl

Piperazine, 1-methyl-4-[4-[4-[3-(4-piperidinylmethoxy)-4-pyridinyl]-1H-pyrazol-1-yl]phenyl]-,hydrochloride

(-20℃)

With Ice Pack

≥ 2 years