CCT241533
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.
CHK2是一种检测点激酶，参与ATM介导的对双链DNA断裂的应答。CHK2抑制剂可以增强遗传毒性癌症疗法的疗效。CCT241533已被证明是一个新的CHK2激酶抑制剂。
在体外：CCT241533抑制CHK2的活性，IC50值为3 nmol/L；在1 mmol/L时对一组激酶表现出最小交叉反应性。在一些细胞系中，CCT241533并不能增强其他基因毒性药物的细胞毒活性[1]。而且，作为已被证明最有效的CHK2抑制剂，CCT241533显示出比对CHK1强的选择性（63倍）以及对hERG弱的抑制活性（IC50 = 22 μM）[2]。
计算模拟：X射线晶体学证实CCT241533结合在CHK2的ATP口袋。总的来说，结合模式和先前的化合物高度一致，保持了所有关键的氢键相互作用。CCT241533有效的原因是2个甲氧基占据了酶的溶剂暴露区域，以及异丙醇取代基与环外NH形成分子内氢键[2]。
临床试验：没有可用的临床数据。
参考文献：
[1]. Anderson VE, Walton MI, Eve PD, Boxall KJ, Antoni L, Caldwell JJ, Aherne W, Pearl LH, Oliver AW, Collins I, Garrett MD. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011, 71(2): 463-72.
[2]. Caldwell JJ, Welsh EJ, Matijssen C, Anderson VE, Antoni L, Boxall K, Urban F, Hayes A, Raynaud FI, Rigoreau LJ, Raynham T, Aherne GW, Pearl LH, Oliver AW, Garrett MD, Collins I. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011, 54(2): 580-90.
| Physical Appearance | A crystalline solid |
| Storage | Store at -20°C |
| M.Wt | 442.48 |
| Cas No. | 1262849-73-9 |
| Formula | C23H27FN4O4 |
| Synonyms | CCT 241533;CCT-241533 |
| Solubility | Soluble in DMSO |
| Chemical Name | (E)-4-fluoro-6-(4-((4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl)amino)-6,7-dimethoxyquinazolin-2(1H)-ylidene)cyclohexa-2,4-dienone |
| SDF | Download SDF |
| Canonical SMILES | CC(C1CNCC1NC2=N/C(NC3=CC(OC)=C(OC)C=C32)=C4C=C(F)C=CC\4=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 |
HeLa和HT-29细胞 |
|
制备方法 |
溶于DMSO。若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
|
反应条件 |
2.2 μmol/L（HeLa细胞），1.7或3 μmol/L（HT-29细胞）；24小时 |
|
实验结果 |
CCT241533增强HeLa细胞（2.2 μmol/L CCT241533）和HT-29细胞（1.7 μmol/L CCT241533）对AG14447的敏感性。在HeLa细胞中，CCT241533（3 μmol/L）与Olaparib联合用药显著增强两者的作用。 |
|
References: [1]. Anderson VE, Walton MI, Eve PD, Boxall KJ, Antoni L, Caldwell JJ, Aherne W, Pearl LH, Oliver AW, Collins I, Garrett MD. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011;71(2):463-72. | |
化学结构
