AZD-5438
(Synonyms: 4-[2-甲基-1-异丙基-1H-咪唑-5-基]-N-[4-(甲磺酰基)苯基]-2-嘧啶胺,AZD 5438;AZD5438) 目录号 : GC12438
A potent inhibitor of CDKs
Cas No.:602306-29-6
Sample solution is provided at 25 µL, 10mM.
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AZD5438 is a potent small molecule inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 with half maximal inhibitory concentration IC50 of 16 nmol/L, 6 nmol/L and 20 nmol/L respectively. AZD5438 has also been found to potently inhibit the human cyclin E/CDK2 complex, the cyclin B1/CDK1 complex and the cyclin A/CDK2 complex with IC50 of 0.006 μM, 0.016 μM and 0.045 μM respectively. In previous studies, AZD5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with IC50 ranging from 0.2 μmol/L to 1.7 μmol/L, in which the phosphorylation of a few proteins, including CDK substrates pRb, nucleolin, protein phosphatase 1a and RNA polymerase II COOH-terminal domain, and cell cycling at G2-M, S and G1 phases were inhibited.
References:
[1]Camidge DR1, Smethurst D, Growcott J, Barrass NC, Foster JR, Febbraro S, Swaisland H, Hughes A. A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemother Pharmacol. 2007 Aug;60(3):391-8. Epub 2006 Nov 18.
[2]Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N, Green S, Growcott J, Barker A, Wilkinson RW. 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. doi: 10.1158/1535-7163.MCT-08-0836. Epub 2009 Jun 9.
| Cell experiment [1]: | |
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Cell lines |
MCF-7 breast cancer cells, |
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Preparation method |
The solubility of this compound in DMSO is >18.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
48 h |
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Applications |
AZD5438 induced cell cycle arrest by inhibiting phosphorylation of cdk-dependent substrates, and exhibited the broad antiproliferative activity against asynchronous LoVo, MCF-7 and SW620 tumor cell lines. AZD5438 showed antiproliferative in a range of tumor cell lines including lung, colorectal, breast, prostate, and hematologic tumors with IC50 ranging from 0.2 μM (MCF-7) to 1.7 μM (ARH-77). |
| Animal experiment [1]: | |
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Animal models |
Female nude mice bearing established BT474c, Colo-205, HX147, PC-3, and SW620 human tumor xenografts |
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Dosage form |
Oral gavage, 37.5–75 mg/kg, once or twice daily for 3 wk |
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Application |
In vivo, oral treatment of AZD5438 significantly inhibited the growth of human tumor xenografts derived from a wide range of different cancer types including breast, colon, lung, prostate, and ovarian with maximum TGI ranging from 38% to 153%. In the SW620 xenograft model, AZD5438 inhibited several cell cycle proteins such as, phH3, phosphonucleolin, PP1a, and several phospho-pRb epitopes in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Byth K F, Thomas A, Hughes G, 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[J]. Molecular cancer therapeutics, 2009, 8(7): 1856-1866. | |
| Cas No. | 602306-29-6 | SDF | |
| 别名 | 4-[2-甲基-1-异丙基-1H-咪唑-5-基]-N-[4-(甲磺酰基)苯基]-2-嘧啶胺,AZD 5438;AZD5438 | ||
| 化学名 | 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine | ||
| Canonical SMILES | CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C | ||
| 分子式 | C18H21N5O2S | 分子量 | 371.46 |
| 溶解度 | ≥ 18.55mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6921 mL | 13.4604 mL | 26.9208 mL |
| 5 mM | 0.5384 mL | 2.6921 mL | 5.3842 mL |
| 10 mM | 0.2692 mL | 1.346 mL | 2.6921 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet