HTH-01-091

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

HTH-01-091 是一种有效、选择性、细胞渗透性、ATP 竞争性 MELK 抑制剂，生化 IC50 为 10.5 nM。

HTH-01-091 is a potent and selective, cell-permeable, ATP-competitive MELK inhibitor with biochemical IC50 of 10.5 nM; displays no significant activity for PIK3CA, mTOR, GSK3A and CDK7 (IC50>600 nM); exhibits substantially improved kinome selectivity in comparison with OTSSP167; induces MELK degradation, but demonstrates poor antiproliferative effects in basal-like breast cancer cell lines.

HTH-01-091 (1 μM) selectively inhibits 4% of the kinases over 90%. HTH-01-091 (0-10 μM, 1 h) is cell permeable and causes MELK degradation.HTH-01-091 (0-10 μM, 3 day) exhibits minor antiproliferative effects in breast cancer cells. Western Blot Analysis Cell Line:MDA-MB-468 cells Concentration:0, 0.1, 1.0, and 10 μM Incubation Time:1 h Result:Reduced MELK protein levels in MDA-MB-468 cells; Dose-dependently decreased MELK pull-down by streptavidin beads, demonstrating that the compound is cell permeable and binds to MELK in an ATP-competitive fashion. Had no effect on ERK1/2 pull-down, showing no binding affinity of HTH-01-091 to ERK1/2. Cell Proliferation Assay Cell Line:MDA-MB-468, BT-549, HCC70, ZR-75-1, MCF7, and T-47D cells Concentration:0, 0.001, 0.01, 0.1, 1.0, and 10 μM Incubation Time:3 day Result:Showed antiproliferative activities in a panel of breast cancer cell lines, including MDA-MB-468, BT-549, HCC70, ZR-75-1, MCF7, and T-47D cells, with IC50 values of 4.00 μM, 6.16 μM, 8.80 μM, >10 μM, 8.75 μM, and 3.87 μM, respectively.

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HTH-01-091 | HTH 01-091 | HTH01-091

PI3K/Akt/mTOR signaling

MELK

MELK

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2000209-42-5

499.436

C26H28Cl2N4O2

>98% (HPLC)

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O=C1N([C@H]2CC[C@H](CN(C)C)CC2)C3=C(CN1)C=NC4=CC=C(C5=CC(Cl)=C(O)C(Cl)=C5)C=C34

9-(3,5-dichloro-4-hydroxyphenyl)-1-((1r,4r)-4-((dimethylamino)methyl)cyclohexyl)-3,4-dihydropyrimido[5,4-c]quinolin-2(1H)-one

(-20℃)

With Ice Pack

≥ 2 years