iMDK

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

iMDK 四分之一水合物是一种有效的 PI3K 抑制剂，可抑制生长因子 MDK（也称为 midkine 或 MK）。 iMDK 四分之一水合物与 MEK 抑制剂协同抑制非小细胞肺癌 (NSCLC)，而不伤害正常细胞和小鼠。

iMDK quarterhydrate is a potent PI3K inhibitor that inhibits the growth factor MDK (also known as midkine or MK). iMDK quarterhydrate synergistically inhibits non-small cell lung cancer (NSCLC) with MEK inhibitors without harming normal cells and mice.(In Vitro):Administration of iMDK (50-500 nM) for 72 h quarterhydrate suppressed AKT phosphorylation in H441 lung adenocarcinoma cells after treatment dose-dependently. In contrast, iMDK quarterhydrate robustly increases p-ERK.(In Vivo):Intraperitoneally injection with 100 μl of iMDK ( (9 mg/kg/day) and ; oral administion of PD0325901 (5 mg/kg) effectively reduced lung tumor growth in a xenograft mouse model.

Cell Viability Assay Cell Line:H441 (lung adenocarcinoma; KRASG12V), H2009 (non-small cell carcinoma; KRASG12A), A549 (lung carcinoma; KRASG12S) and H520 (lung squamous cell carcinoma; KRASWT) Concentration:iMDK (2.5 μM) and PD0325901 (0.5 μM) for H441 and H2009 cells iMDK (0.125 μM) and PD0325901 (0.25 μM) for H520 cells iMDK (0.25 μM) and PD0325901 (0.125 μM) for A549 cells Incubation Time:72 hours Result:iMDK alone did not inhibit cell viability of A549 cells, the combinatorial treatment of iMDK with PD0325901 significantly inhibited that of A549 cells compared to the single treatment of PD0325901.Western Blot Analysis Cell Line:H441 lung adenocarcinoma cells Concentration:0-500 nM Incubation Time:72 hours Result:Suppressed AKT phosphorylation in a dose-dependent manner.ERK1/2 phosphorylation was increased.

Animal Model:female BALB/c nude mice (6 week old) bearing H441 human lung cancer xenografts Dosage:iMDK (9 mg/kg) and PD0325901 (5 mg/kg) Administration:Intraperitoneally injected with 100 μL iMDK everyday and/or orally administered PD0325901 five times per week (on days 1, 2, 3, 4, 5, 7, 8, 9, 10, 11)Result:Reduced significantly volume of the tumors derived from H441 lung adenocarcinoma cells after the combination treatment with iMDK and PD0325901 compared to that of single compound in a xenograft mouse model.

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PI3K/Akt/mTOR signaling

PI3K

TRPV1

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881970-80-5

376.41

C21H13FN2O2S

>98% (HPLC)

In Vitro:?DMSO : 3.33 mg/mL (8.85 mM)

Fc1ccc(Cc2cn3cc(nc3s2)-c2cc3ccccc3oc2=O)cc1

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(-20℃)

With Ice Pack

≥ 2 years