CCT241533 hydrochloride
(Synonyms: CCT241533盐酸盐,CCT-241533 hydrochloride;CCT 241533 hydrochloride) 目录号 : GC17105
A selective Chk2 inhibitor
Cas No.:1431697-96-9
Sample solution is provided at 25 µL, 10mM.
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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 inhibited CHK2 with an IC50 of 3 nmol/L and showed 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 showed potent selectivity (63-fold) over CHK1 and low hERG inhibition [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 appeared 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 [2].
Clinical trial: No clinical data are available currently
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.
Cell experiment: | HT-29, HeLa and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combination with increasing concentrations of either PARP inhibitor or cytotoxic drug in a 96 hour SRB assay or 7-10 day colony forming assay. The ability of CCT241533 to enhance cell killing is expressed as a potentiation index (PI) which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARP inhibitor in combination with a CHK2 inhibitor. Thus PI>1 indicates potentiation and PI<1 indicates protection[1]. |
References: [1]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72. | |
| Cas No. | 1431697-96-9 | SDF | |
| 别名 | CCT241533盐酸盐,CCT-241533 hydrochloride;CCT 241533 hydrochloride | ||
| 化学名 | (6Z)-4-fluoro-6-[4-[[(3S,4R)-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl]amino]-6,7-dimethoxy-1H-quinazolin-2-ylidene]cyclohexa-2,4-dien-1-one;hydrochloride | ||
| Canonical SMILES | CC(C)(C1CNCC1NC2=NC(=C3C=C(C=CC3=O)F)NC4=CC(=C(C=C42)OC)OC)O.Cl | ||
| 分子式 | C23H28ClFN4O4 | 分子量 | 478.94 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 5 mg/ml,PBS (pH 7.2): 500 µ g/ml | 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 | 2.0879 mL | 10.4397 mL | 20.8794 mL |
| 5 mM | 0.4176 mL | 2.0879 mL | 4.1759 mL |
| 10 mM | 0.2088 mL | 1.044 mL | 2.0879 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