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AZD-5438

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Chemical Structure| 602306-29-6 同义名 : -
CAS号 : 602306-29-6
货号 : A457556
分子式 : C18H21N5O2S
纯度 : 99%+
分子量 : 371.457
MDL号 : MFCD11112135
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(282.67 mM)，配合低频超声助溶，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：
生物活性
靶点

  • CDK2

    CDK2, IC50:6 nM

  • CDK9

    CDK9, IC50:20 nM

  • CDK1

    CDK1, IC50:16 nM
描述 The regulatory proteins that control cell cycle progression are the cyclins, cyclin-dependent kinases (cdks). Cdk inhibitors preferentially target proliferating cells and induce cell death, thus making cdks among the most highly attractive targets for therapeutic intervention in cancer. AZD5438 is a potent inhibitor of cdk 1, 2, and 9 with IC50 values of 16, 6, and 20 nM, respectively. In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines with an IC50 value ranging from 0.2 to 1.7 μM, causing inhibition of the phosphorylation of cdk substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain and blocking cell cycling at G2-M, S, and G1 phases. In vivo, when orally administered at either 50 mg/kg twice daily or 75 mg/kg once daily, AZD5438 inhibited human tumor xenograft growth (maximum percentage tumor growth inhibition, range, 38-153; P < 0.05)[3]. In human xenograft animal models using athymic nude mice, combined treatment with AZD5438 and irradiation enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7[4].
作用机制 There is a hydrogen-bonding interaction between imidazole of AZD5438 and the hinge region of cdks[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
human LoVo cells Proliferation assay 48 h Antiproliferative activity against human LoVo cells assessed as BrdU incorporation after 48 hrs, IC50=0.63 μM 18815031
human LoVo cells Proliferation assay 48 h Antiproliferative activity against human LoVo cells assessed as inhibition of BrdU incorporation after 48 hrs, IC50=0.8 μM 18996007
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00088790 Neoplasms Phase 1 Completed - United States, Massachusetts ... 展开 >> Research Site Boston, Massachusetts, United States United States, New York Research Site New York City, New York, United States 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.69mL

0.54mL

0.27mL

13.46mL

2.69mL

1.35mL

26.92mL

5.38mL

2.69mL
参考文献

[1]Raghavan P, Tumati V, et al. AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e507-14.

[2]Byth KF, Thomas A, et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66.

[3]Byth KF, Thomas A, et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66

[4]Raghavan P, Tumati V, et al. AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells. Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e507-14