AZD-5438
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
AZD5438是一种有效的细胞周期蛋白依赖性激酶(CDK)1、2和9的小分子抑制剂,IC50值分别为16 nmol/L、6 nmol/L和20 nmol/L。AZD5438也有效抑制人cyclin E/CDK2复合体,cyclin B1/CDK1复合体和cyclin A/CDK2复合体,IC50值分别为0.006 μM、0.016 μM和0.045 μM。据报道,AZD5438在少数人类肿瘤细胞系中具有显著的抗增殖活性,IC50范围介于0.2 μmol/L到1.7 μmol/L之间,AZD5438也抑制几个蛋白的磷酸化,包括CDK底物pRb、nucleolin、蛋白磷酸酶1a和RNA聚合酶II COOH-端结构域,并诱导G2-M、S和G1细胞周期停滞。
参考文献:
[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.
- 1. Cingöz O, Goff SP. "Cyclin-dependent kinase activity is required for type I interferon production." Proc Natl Acad Sci U S A. 2018 Mar 27;115(13):E2950-E2959. PMID:29507205
- 2. Yuan J, Jiang YY, et al. "Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma." Cancer Res. 2017 Dec 1;77(23):6614-6626. PMID:28951465
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 371.46 |
Cas No. | 602306-29-6 |
Formula | C18H21N5O2S |
Synonyms | AZD 5438;AZD5438 |
Solubility | insoluble in H2O; ≥18.55 mg/mL in DMSO; ≥42.1 mg/mL in EtOH |
Chemical Name | 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine |
SDF | Download SDF |
Canonical SMILES | CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验 [1]: | |
细胞系 |
MCF-7乳腺癌细胞 |
溶解方法 |
该化合物在DMSO中的溶解度大于18.6 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
48 h |
应用 |
AZD5438通过抑制cdk依赖性底物的磷酸化诱导细胞周期停滞,针对异步LoVo、MCF-7和SW620肿瘤细胞系具有广泛的抗增殖活性。在包括肺、结肠直肠、乳腺、前列腺和血液肿瘤的一系列肿瘤细胞系中,AZD5438显示出抗增殖活性,IC50范围为0.2 μM(MCF-7)至1.7 μM(ARH-77)。 |
动物实验 [1]: | |
动物模型 |
携带BT474c、Colo-205、HX147、PC-3和SW620人肿瘤异种移植物的雌性裸鼠模型 |
给药剂量 |
口服,37.5–75 mg/kg,每天一次或两次,持续3周 |
应用 |
在体内,口服AZD5438显著抑制各种人肿瘤异种移植物的生长,包括乳腺癌、结肠癌、肺癌、前列腺癌和卵巢癌,最大TGI范围为38%至153%。在SW620异种移植模型中,AZD5438以剂量依赖的方式抑制几种细胞周期蛋白,如phH3、phosphonucleolin、PP1a和几种磷酸化-pRb表位。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
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. |
描述 | AZD5438是一种有效的CDK1/2/9抑制剂,IC50值为16 nM/6 nM/20 nM。 | |||||
靶点 | CDK1 | CDK2 | CDK9 | |||
IC50 | 16 nM | 6 nM | 20 nM |
质量控制和MSDS
- 批次: