LY2603618
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.
LY2603618是一种新型小分子检测点激酶1(Chk1)抑制剂,具有直接的抗肿瘤效应[1],也可使肿瘤细胞对DNA损伤化疗治疗脱敏[2]。
检查点激酶1(Chk1)是一种协调受损DNA修复的激酶类型[1]。已经发现一些肿瘤细胞具有过量的Chk1,其使细胞对DNA靶向化疗脱敏,促进肿瘤增殖[3]。
LY2603618通过与ATP分子竞争抑制Chk1 [2]。在A549和H1299非小细胞癌细胞系中,致死浓度的LY2603618(10 μM)不仅导致细胞增殖停滞, G2/M期细胞数量从13%增加至38%,而且导致DNA损伤。H2AX磷酸化的增加表明DNA损伤 [1]。
在体内实验以确定LY2603618与其他化疗的组合效果[2]。在Calu-6肺癌细胞小鼠异种移植模型中,注射吉西他滨150 mg/kg和口服摄取LY2603618(200 mg/kg)共同作用增加肿瘤的DNA损伤,与用吉西他滨单独治疗的小鼠相比,Chk1 s345磷酸化增加2倍[2]。
参考文献:
[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.
- 1. Qiu Z, Fa P, et al. "A genome-wide pooled shRNA screen identifies PPP2R2A as a predictive biomarker for the response to ATR and CHK1 inhibitors." Cancer Res. 2020;canres.0057.2020. PMID:32522823
- 2. Yenerall P, Das AK, et al. "RUVBL1/RUVBL2 ATPase Activity Drives PAQosome Maturation, DNA Replication and Radioresistance in Lung Cancer." Chem Biol. 2020;27(1):105–121.e14. PMID:31883965
- 3. Yang X, Pan Y, et al. "RNF126 as a biomarker of a poor prognosis in invasive breast cancer and CHK1 inhibitor efficacy in breast cancer cells." Clin Cancer Res. 2018 Jan 11. pii: clincanres.2242.2017. PMID:29326282
- 4. Höhn A, Krüger K, et al. "Distinct mechanisms contribute to acquired cisplatin resistance of urothelial carcinoma cells." Oncotarget. 2016 Jul 5;7(27):41320-41335. PMID:27191498
- 5. Zhang Y, Lai J, et al. "Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stress." Oncotarget. 2016 Jun 7;7(23):34688-702. PMID:27167194
Storage | Store at -20°C |
M.Wt | 436.3 |
Cas No. | 911222-45-2 |
Formula | C18H22BrN5O3 |
Solubility | ≥43.6 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH |
Chemical Name | 1-[5-bromo-4-methyl-2-[[(2S)-morpholin-2-yl]methoxy]phenyl]-3-(5-methylpyrazin-2-yl)urea |
SDF | Download SDF |
Canonical SMILES | CC1=CC(=C(C=C1Br)NC(=O)NC2=NC=C(N=C2)C)OCC3CNCCO3 |
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宫颈癌细胞,Calu-6非小细胞肺癌细胞,HT29和HCT-116结肠癌细胞 |
溶解方法 |
该化合物在DMSO中的溶解度大于21.8 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
1250 nM,2500 nM,24 h |
应用 |
LY2603618 (1250 nM)明显减少G1群体细胞数目,增加晚S期细胞数目。LY2603618(5000 nM)导致细胞处于S期,DNA含量介于2和4N之间。LY2603618诱导DNA损伤并阻止DNA合成,同时增加表达有丝分裂早期标志物的细胞数量。LY2603618导致细胞缺乏正常的有丝分裂。 LY2603618使pH3(S10)染色细胞的比例增加,相比于对照细胞,诱导异常前中期阻滞。LY2603618增加gemcitabine在p53突变体HT-29细胞中的效力,但不增加其在野生型p53 HCT-116细胞中的功效。 |
动物实验 [1]: | |
动物模型 |
携带Calu-6异种移植物的雌性Harlan无胸腺裸鼠 |
给药剂量 |
口服,200 mg/kg |
应用 |
在Calu-6肿瘤异种移植模型中,LY2603618有效抑制gemcitabine激活的Chk1,而对ATR的激活没有影响。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
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. |
Description | LY2603618 is a selective inhibitor of Chk1 with potential anti-tumor activity. | |||||
Targets | Chk1 | |||||
IC50 |
质量控制和MSDS
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