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JNJ-7706621

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Chemical Structure| 443797-96-4 同义名 : Aurora A Inhibitor I;Aurora Kinase/CDK Inhibitor
CAS号 : 443797-96-4
货号 : A262123
分子式 : C15H12F2N6O3S
纯度 : 99%+
分子量 : 394.356
MDL号 : MFCD11100270
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(304.29 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 10 mg/mL clear

PO 0.5% CMC-Na 52 mg/mL suspension

生物活性
靶点

  • Aurora A

    Aurora A, IC50:11 nM

  • Aurora B

    Aurora B, IC50:15 nM

  • CDK4

    CDK4/CyclinD1, IC50:253 nM

  • CDK2

    CDK2/CyclinE, IC50:3 nM

    CDK2/CyclinA, IC50:4 nM
描述 Cyclin-dependent kinases (CDKs) are a family of serine/threonine protein kinases that participate in cell cycle regulation. The functionally distinct kinase complexes are formed by the combination of catalytic kinase subunits (such as CDK1, CDK2, CDK4, or CDK6) with regulatory cyclin subunits (such as cyclin A, B, D1, D2, D3, or E). Coordinated activation of these complexes at specific times drives cells through the cell cycle and ensures the fidelity of cell division. The Aurora kinases also have a critical role in controlling chromosome movement and organization, thus regulating cell cycle. Aurora-A contributes to formation of the mitotic spindle apparatus that guarantees accurate segregation of chromosomes into daughter cells; Aurora-B is required for cytokinesis and proper chromosome architecture during mitosis. JNJ-7706621 is a dual CDK and aurora inhibitor. Based on results from in vitro kinase assays utilizing human recombinant enzymes, JNJ-7706621 inhibited CDK1/Cyclin B, CDK2/Cyclin A, CDK2/Cyclin E, Aurora-A and Aurora-B with IC50s of 9 nM, 4 nM, 3 nM, 11 nM and 15 nM, respectively. JNJ-7706621 showed potent growth inhibition in vitro on human cancer cell lines of Hela, HCT-116, SKOV-3, PC3, A375, MDA-MB-231, DU145 with IC50 values ranging from 112 to 514 nM. Cell cycle analysis on Hela cells synchronized in G1 showed that cells treated with 3 μM JNJ-7706621 did not enter the S phase until 16 hours after G1 synchronization, indicating that JNJ-7706621 delayed exit from G1 and arrested cells in G2-M. In a human tumor xenograft model established by implantation of A375 tumor fragments in female nu/nu mice, JNJ-7706621 given i.p. when the tumors reached approximately 62 to 126 mg at the dose of 125 mg/kg with the 7 on/7 off schedule or the 100 mg/kg daily schedule both produced identical tumor growth inhibition values of 93%[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
HCT116 cells Function assay In vitro inhibitory concentration against cell proliferation in human HCT116 (colon carcinoma) tumor cells, IC50=0.25 μM 15974571
human A375 cells Proliferation assay Antiproliferative activity against human A375 cells, IC50=0.447 μM 16682186
human HeLa cells Function assay In vitro inhibitory concentration against cell proliferation in human HeLa (cervical adenocarcinoma) tumor cells, IC50=0.28 μM 15974571
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.54mL

0.51mL

0.25mL

12.68mL

2.54mL

1.27mL

25.36mL

5.07mL

2.54mL
参考文献

[1]Seamon JA, Rugg CA, et al. Role of the ABCG2 drug transporter in the resistance and oral bioavailability of a potent cyclin-dependent kinase/Aurora kinase inhibitor. Mol Cancer Ther. 2006 Oct;5(10):2459-67.

[2]Emanuel S, Rugg CA, et al. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Cancer Res. 2005 Oct 1;65(19):9038-46.

[3]Emanuel S, Rugg CA, Gruninger RH, Lin R, Fuentes-Pesquera A, Connolly PJ, Wetter SK, Hollister B, Kruger WW, Napier C, Jolliffe L, Middleton SA. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Cancer Res. 2005 Oct 1;65(19):9038-46.