LY2606368
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.
LY2606368是一种选择性的和ATP竞争性的检查点激酶1(CHK1)抑制剂,在SW1990细胞中的IC50值为1.5 nM[1]。
CHK1是一种丝氨酸/苏氨酸激酶,在DNA损伤应答途径中起重要作用。CHK1的抑制剂被用于癌症治疗。
LY2606368是一种ATP竞争性的CHK1抑制剂,目前正处于临床阶段。在癌细胞中,LY2606368抑制CHK1的自磷酸化,诱导H2AX的磷酸化。在胰腺癌细胞系SW1990中,LY2606368显著抑制细胞增殖,IC50值为1.5 nM。在SW1990异种移植模型中,SW1990具有有效的抗肿瘤活性。除此之外,在SKVO3原位移植肿瘤模型中,LY2606368抑制肿瘤生长,减少肿瘤转移的发生率。然而,由于其较差的口服生物利用度,LY2606368只能通过静脉给药[1,2,3]。
参考文献:
[1] Wu W, Bi C, Bence A K, et al. Antitumor activity of Chk1 inhibitor LY2606368 as a single agent in SW1990 human pancreas orthotopic tumor model. Cancer Research, 2012, 72(8 Supplement): 1776.
[2] Lainchbury M, Matthews T P, McHardy T, et al. Discovery of 3-alkoxyamino-5-(pyridin-2-ylamino) pyrazine-2-carbonitriles as selective, orally bioavailable CHK1 inhibitors. Journal of medicinal chemistry, 2012, 55(22): 10229-10240.
[3] McNeely S C, Burke T F, DurlandBusbice S, et al. Abstract A108: LY2606368, a second generation Chk1 inhibitor, inhibits growth of ovarian carcinoma xenografts either as monotherapy or in combination with standard-of-care agents. Molecular Cancer Therapeutics, 2011, 10(Supplement 1): A108.
Storage | Store at -20°C |
M.Wt | 365.39 |
Cas No. | 1234015-52-1 |
Formula | C18H19N7O2 |
Synonyms | Prexasertib |
Solubility | insoluble in DMSO |
Chemical Name | 5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile |
SDF | Download SDF |
Canonical SMILES | NCCCOC1=CC=CC(OC)=C1C2=CC(NC(C=N3)=NC=C3C#N)=NN2 |
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细胞 |
制备方法 |
溶解度有限,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 |
7 h |
实验结果 |
LY2606368触发S期DNA损伤,如pH2AX(S139)和TUNEL阳性染色细胞在S期细胞中显著增加。LY2606368也需要CDC25A和CDK2来触发DNA损伤。此外,LY2606368导致复制灾变。 |
动物实验: [1] | |
动物模型 |
携带Calu-6肿瘤的雌性CD-1nu-/nu小鼠(26-28 g) |
给药剂量 |
1、3.3或10 mg/kg,每天两次,持续3天 |
实验结果 |
在所测试的三个剂量LY2606368组中观察到高达72.3%的肿瘤生长抑制,小鼠的体重下降不超过3%,表明LY2606368在任何治疗组中耐受性良好。此外,在28天恢复期间,最高剂量组的肿瘤再生长缓慢,表明肿瘤对LY2606368产生持久应答。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: 1. King C, Diaz HB, McNeely S et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-13. |
质量控制和MSDS
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