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CCT241533

现货
Catalog No.
A3291
有效的Chk2抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,400.00
Ship with 10-15 days
10mg
¥ 2,660.00
Ship with 10-15 days
50mg
¥ 7,600.00
Ship with 10-15 days
100mg
¥ 11,400.00
Ship with 10-15 days

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Background

CHK2 is a checkpoint kinase involved in the ATM-mediated response to double-strand DNA breaks. Inhibitors of CHK2 may increase the efficacy of genotoxic cancer therapies. CCT241533 has been identified and characterized as a novel CHK2 kinase inhibitor.

In vitro: CCT241533 inhibits CHK2 with an IC50 of 3 nmol/L and shows minimal cross-reactivity against a panel of kinases at 1 mmol/L. CCT241533 did not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines [1]. Moreover, as the most potent CHK2 inhibitor identified in the series, CCT241533 shows potent selectivity (63-fold) over CHK1 and low hERG inhibition (hERGIC50=22 μM) [2].

In silico: X-ray crystallography confirmed that CCT241533 bound to CHK2 in the ATP pocket. Overall, the binding mode was found to be very highly conserved relative to previous compounds, with all of the key hydrogen bond interactions maintained. The potency gained with CCT241533 therefore appears to be due to the presence of the two methoxy substituents occupying the solvent exposed region of the enzyme, and contributions from the isopropyl alcohol substituent, which may participate in a second intramolecular hydrogen bond to the quinazoline exocyclicNH [2].

Clinical trial: No clinical data are available.

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.
[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.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt442.48
Cas No.1262849-73-9
FormulaC23H27FN4O4
SynonymsCCT 241533;CCT-241533
SolubilitySoluble 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
SDFDownload SDF
Canonical SMILESCC(C1CNCC1NC2=N/C(NC3=CC(OC)=C(OC)C=C32)=C4C=C(F)C=CC\4=O)(O)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

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.

质量控制

质量控制和MSDS

批次:

化学结构

CCT241533