1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEINH154Cat. No.: HY-117154CAS No.: 1587705-63-2分式: CHNOS分量: 392.52作靶點(diǎn): Others作通路: Others儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 62.5 mg/mL (159.23 mM; Need ultrasonic)H2O : 40% PEG30

2、0 5% Tween-80 45% salineSolubility: 2.08 mg/mL (5.30 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (5.30 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 INH154Nek2 和 Hec1 結(jié)合的效抑制劑 (INH)，其在 Hela 和 MB468 細(xì)胞中的 IC50 值分別為 200 nM 和12

3、0 nM。IC50 & Target IC50: 200 nM (INH in Hela cells), 120 nM (INH in MB468 cells) 1.體外研究 INH154 is highly potent in treating breast tumors with co-elevated expression of Hec1 and Nek2. INH154 isthe most potent inhibitor of tumor cell growth. The IC50 values of INH154 in HeLa and MDA-MB-468 cancercell

4、s are 0.20 and 0.12 M, respectively. INH154 also suppresses the growth of leukemia, osteosarcoma,and glioblastoma cells 1.體內(nèi)研究 Tumor growth rates in mice treated with INH154 are evidently slower than those in control animals in a dose-dependent manner. In agreement with the tumor-growth data, the tu

5、mor proliferation index, determined bymeasuring BrdU staining, is clearly reduced in residual tumors treated with INH154 in comparison withvehicle alone. The expression levels of Nek2 and Hec1 S165 phosphorylation are also substantially reducedin INH154-treated tumors than in vehicle-treated tumors.

6、 On the other hand, mice body weights aremeasured during the 6.5 weeks treatment period and show little difference among treated and controlgroups. In addition, the toxicity of INHs by treating normal BALB/c ByJNarl mice with high dosage of INH154(20 mg/kg) shows no significant difference of body we

7、ights, blood chemistry, and complete blood count(CBC) analysis among these groups of animals 1.PROTOCOLAnimal Mice 1Administration 1 Human triple negative breast cancer MDA-MB-468 cells, which expressed high levels of both Hec1 andNek2, are used to test the efficacy of tumor growth in mouse xenograf

8、t. While tumor volumes reach100mm3, mice are randomly divided into 5 treatment groups and began to receive thrice-weeklyintraperitoneal (i.p.) injections of vehicle control, 10 mg/kg INH41, 50 mg/kg INH41, 5 mg/kg INH154 or 20mg/kg INH154. Treatment is continued for 6.5 weeks and the tumor sizes wer

9、e measured 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Hu CM, et al. Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation througha death-trap mechanism. Oncogene. 2015 Mar 5;34(10):1220-30.McePdfHeightCaution: Product has not been fully validated for medi