MELK-T1 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

一种新型、细胞渗透性、强效、选择性的 MELK 激酶结构域抑制剂，IC50 为 37 nM。

A novel, cell-permeable, potent and selective inhibitor of MELK kinase domain with IC50 of 37 nM; shows >50% inhibition at 1 uM against 6 kianses in a panel of 235 kinases (Flt3 IC50=18 nM); triggers a rapid and proteasome-dependent degradation of the MELK protein, induces the accumulation of stalled replication forks and DSBs in MCF-7 cells; induces a strong phosphorylation of p53, a prolonged up-regulation of p21 and a down-regulation of FOXM1 target genes.

JNJ-47117096 hydrochloride is potent and selective MELK inhibitor, with an IC50 of 23 nM, also effectively inhibits Flt3, with an IC50 of 18 nM, and slighitly blocks CAMKIIδ, Mnk2, CAMKIIγ, and MLCK (IC50, 810 nM, 760 nM, 1000 nM, 1000 nM). JNJ-47117096 (MELK-T1) suppresses the proliferation of Flt3-driven Ba/F3 cell lines, with an IC50 of 1.5 μM in the absence of IL-3, while no inhibitory activity is observed in the presence of IL-3. JNJ-47117096 does not inhibit the proliferation of Ba/F3 cell lines transfected with either FGFR1, FGFR3, or KDR, either in the presence or absence of IL-3. JNJ-47117096 (MELK-T1, 10 μM) delays the progression of MCF-7 cells through S-phase. JNJ-47117096 inhibits MELK, and then exerts stalled replication forks and DNA double-strand breaks (DSBs). JNJ-47117096 activates the ATM-mediated DNA-damage response (DDR). JNJ-47117096 (3, 10 μM) results in a growth arrest and a senescent phenotype. Moreover, JNJ-47117096 induces a strong phosphorylation of p53, a prolonged up-regulation of p21 and a down-regulation of FOXM1 target genes.

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PI3K/Akt/mTOR signaling

MELK

MELK

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1610536-69-0

398.891

C21H23ClN4O2

>98% (HPLC)

DMSO : ≥ 250 mg/mL 626.74 mM

COC1=C(C=CC(=C1)C2=CNN=C2)C(=O)NC3=CC4=C(CCNCC4)C=C3.Cl

2-methoxy-4-(1H-pyrazol-4-yl)-N-(2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)benzamide hydrochloride

(-20℃)

With Ice Pack

≥ 2 years