ZT-12-037-01

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

ZT-12-037-01 是一种有效的、选择性的、ATP 竞争性 STK19 抑制剂，以 NRAS 磷酸化百分比测量的 IC50 为 20.04 nM。

ZT-12-037-01 is a potent, selective, ATP-competitive STK19 inhibitor with IC50 of 20.04 nM measured as percentage of NRAS phosphorylation; shows similar IC50 of 23.96 and 27.94 nM for STK19WTWT STK19D89N respectively; displays extremely high kinase selectivity using KINOMEscan against a panel of 468 diverse kinases using an in vitro ATP-site competition binding assay at 1 uM; efficiently inhibits phosphorylation of NRAS in a dose- and time-dependent manner, inhibits NRAS activity in a dose-dependent manner but does not affect the levels of H3K9 methylation; effectively inhibits NRAS signaling, including the MEK-ERK and PI3K pathways in SK-MEL-2 and WM2032 cells (with NRASQ61R), but the inhibition was much less effective in A375 or UACC62 cells (with NRASWT), effectively inhibits cell growth and induces apoptosis of SK-MEL-2 and WM2032 melanoma cells.

Cell Proliferation Assay Cell Line:CDK4 (R24C) melanocyte cells; hTERT melanocyte cells; p53DD melanocyte cells Concentration:3 μM Incubation Time:14 days Result:Inhibited melanocyte proliferation.Western Blot Analysis Cell Line:STK19WT and STK19D89N Concentration:0 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Time: Result:Inhibited NRAS phosphorylation.

Animal Model:SK-MEL-2 xenograft melanoma nude mice with hTERT/p53DD/CDK4(R24C) melanocytes Dosage:25 mg/kg; 50 mg/kg Administration:Intraperitoneally injection; 21 days; once a day Result:Inhibited growth of SK-MEL-2 xenograft melanoma.

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MAPK/ERK Signaling

Ras

Ras

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2328073-61-4

385.512

C21H31N5O2

>98% (HPLC)

In Vitro:?1M HCl : 100 mg/mL (259.40 mM)

COC1=CC2=NC(NC3CC3)=NC(NC4CCN(C(C)C)CC4)=C2C=C1OC

N2-cyclopropyl-N4-(1-isopropylpiperidin-4-yl)-6,7-dimethoxyquinazoline-2,4-diamine

(-20℃)

With Ice Pack

≥ 2 years