AT7519 Hydrochloride
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.
IC50: AT7519在人肿瘤细胞系中有强效抗增殖活性(40-940 nmol/L)。
细胞周期蛋白依赖性激酶(CDK)在真核细胞生长、分裂及死亡中起核心作用。它在细胞周期进程中的重要作用和在几种人类癌症中的失调使他们成为有吸引力的治疗肿瘤的靶点。开发了一系列CDK抑制剂,其中AT7519目前正用于早期临床开发阶段。
体外:AT7519在各种人类肿瘤细胞中有强效抗增殖活性(40-940 nmol/L),其作用机制与对CDK1和CDK2的抑制一致。AT7519引起细胞周期停滞,随后引起人肿瘤细胞凋亡,且抑制人肿瘤异种移植模型中的肿瘤生长[1]。
体内:在HCT116和HT29结肠癌异种移植模型中,AT7519每天两次给药可诱导肿瘤消退。这些效应与CDKs的体内抑制及AT7519诱导的肿瘤细胞凋亡相关[1]。
临床试验:对AT7519进行临床I期药代动力学与药效学研究,AT7519是一种细胞周期蛋白依赖性激酶抑制剂,用于难治性实体肿瘤患者。心电图检查表明QTc剂量依耐性增加,未确定最大耐受剂量就中断募集。4例患者病情稳定6个月以上,1例患者具有延长的部分反应。药代动力学特性表明,随着剂量的增加,线性暴露仅有最适度的患者间变化。由于CDK的抑制作用(其剂量低于QTc间期延长DLT出现的剂量),AT7519引发临床和PD活性[2]。
参考文献:
[1] Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009;8(2):324-32.
[2] Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol. 2011;22(9):2137-43.
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 418.71 |
Cas No. | 902135-91-5 |
Formula | C16H18Cl3N5O2 |
Synonyms | AT 7519 Hydrochloride;AT-7519 Hydrochloride |
Solubility | ≥29.93 mg/mL in H2O; ≥43.3 mg/mL in DMSO with ultrasonic; ≥8.82 mg/mL in EtOH with ultrasonic |
Chemical Name | 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide;hydrochloride |
SDF | Download SDF |
Canonical SMILES | C1CNCCC1NC(=O)C2=C(C=NN2)NC(=O)C3=C(C=CC=C3Cl)Cl.Cl |
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。 |
质量控制和MSDS
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