LY2603618
(Synonyms: LY2603618; IC-83) 目录号 : GC15741
A Chk1 inhibitor
Cas No.:911222-45-2
Sample solution is provided at 25 µL, 10mM.
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LY2603618 is a novel small molecular checkpoint kinase 1 (Chk1) inhibitor that has direct anti-tumour effect [1], as well as desensitizing tumour cell against DNA-damaging chemotherapy treatment [2].
Checkpoint kinase 1 (Chk1) is a type of kinase that coordinates damaged-DNA repair [1]. Some tumour cells have been found to possess over-regulated populations of Chk1 that desensitize the cell from DNA-targeting chemotherapy, promoting tumour proliferation [3].
LY2603618 inhibits Chk1 by competing with ATP molecules [2]. In A549 and H1299 non-small cancer cell lines, lethal concentration of LY2603618 (10 µM) not only resulted in cell proliferation arrest (increase population of cell at G2/M phase from 13% to 38%) but also directly DNA damage, the latter of which was indicated by the increasing occurrence of H2AX phosphorylation[1].
In vivo, experiment was carried out to determine the combining effect of LY2603618 with other chemotherapy[2] . In mice xenograft model that inculated with Calu-6 lung cancer cell, combining administration of injected gemcitabine 150 mg/kg and orally uptake LY2603618 (200 mg/kg) resulted in increased DNA damage of tumour, as was demonstrated by a 2-fold increase in Chk1 s345 phosphorylation in comparison with mice treated with gemcitabine alone[2].
References:
[1]. Wang F Z, Fei H R, Cui, Y J et al. The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells. Apoptosis, 2014,19:1389-1398.
[2]. King C, Diaz H, Barnard D et al.Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs, 2014, 32: 213-26.
[3]. Zhang Y. & Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer, 2014. 134: 1013-23.
| Cell experiment [1]: | |
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Cell lines |
HeLa cervical cancer cells, Calu-6 non-small cell lung cancer cells, HT29 and HCT-116 colon cancer cells |
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Preparation method |
The solubility of this compound in DMSO is >21.8mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1250 nM, 2500 nM, 24 h |
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Applications |
Treatment with 1250 nM LY2603618 resulted in a clear decrease in the G1 population and an increase in late S-phase cells. Cells treated with 5000 nM LY2603618 were predominantly found in the S-phase peak with a DNA content intermediate between 2 and 4N. LY2603618 induced DNA damage and arrested DNA synthesis while increasing the number of cells expressing an early marker of mitosis. LY2603618 treated cells lacked normal mitotic cells. An increased proportion of LY2603618 treated cells stained for pH3(S10) and were arrested in an abnormal prometaphase relative to the control cells. LY2603618 increased the potency of gemcitabine in p53-mutant HT-29 cells, but not in p53 WT HCT-116 cells |
| Animal experiment [1]: | |
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Animal models |
Female Harlan athymic nude mice bearing Calu-6 xenografts |
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Dosage form |
Oral administration, 200 mg/kg |
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Application |
LY2603618 effectively inhibited the activation of Chk1 but not ATR by gemcitabine in Calu-6 tumor xenografts. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. King C, Diaz H, Barnard D, et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor[J]. Investigational new drugs, 2014, 32(2): 213-226. |
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| Cas No. | 911222-45-2 | SDF | |
| 别名 | LY2603618; IC-83 | ||
| 化学名 | 1-[5-bromo-4-methyl-2-[[(2S)-morpholin-2-yl]methoxy]phenyl]-3-(5-methylpyrazin-2-yl)urea | ||
| Canonical SMILES | CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3 | ||
| 分子式 | C18H22BrN5O3 | 分子量 | 436.3 |
| 溶解度 | ≥ 43.6mg/mL in DMSO with gentle warming | 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 | 2.292 mL | 11.46 mL | 22.92 mL |
| 5 mM | 0.4584 mL | 2.292 mL | 4.584 mL |
| 10 mM | 0.2292 mL | 1.146 mL | 2.292 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet