G007-LK
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.
G007-LK是tankyrase 1/2的有效特异性抑制剂,IC50值分别为46和25 nM[1].
端粒重复因子1(TRF1)相互作用锚蛋白相关ADP-核糖聚合酶1 (tankyrase 1,TNKS1)和tankyrase 2 (TNKS2)属于多聚(ADP-核糖)聚合酶亚家族,参与调节大聚合结构的组装和去组装[1].
G007-LK是tankyrase 1/2的有效特异性抑制剂.G007-LK减少TNKS1和TNKS2的自聚ADP-核糖基化,IC50值分别为46和25 nM.在Wnt3a诱导的HEK293细胞中,G007-LK抑制ST-Luc,IC50值为0.05 μM[1].在转染GFP-TNKS1的SW480结直肠癌细胞系中,G007-LK诱导包含磷酸化β-连环蛋白\β-TrCP和泛素的高度动态和移动的降解体[2].在APC突变细胞系中,G007-LK降低胞质和核中β连环蛋白的含量[3].
在COLO-320DM细胞异种移植小鼠中,G007-LK(20 mg/kg每天两次或40 mg/kg每天一次)浓度依赖性地抑制肿瘤生长,分别抑制61%和48%.此外,G007-LK降低TNKS1/2和β连环蛋白的水平,稳定AXIN1/2[3].
参考文献:
[1]. Voronkov A, Holsworth DD, Waaler J, et al. Structural basis and SAR for G007-LK, a lead stage 1,2,4-triazole based specific tankyrase 1/2 inhibitor. J Med Chem, 2013, 56(7): 3012-3023.
[2]. Thorvaldsen TE, Pedersen NM, Wenzel EM, et al. Structure, Dynamics and Functionality of Tankyrase Inhibitor-induced Degradasomes. Mol Cancer Res, 2015, pii: molcanres.0125.2015.
[3]. Lau T, Chan E, Callow M, et al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res, 2013, 73(10): 3132-3144.
- 1. Leibold J, Ruscetti M, et al. "Somatic Tissue Engineering in Mouse Models Reveals an Actionable Role for WNT Pathway Alterations in Prostate Cancer Metastasis." Cancer Discov. 2020;10(7):1038-1057.nbsp;PMID:32376773
- 2. Kim S, Han S, et al. "Tankyrase inhibition preserves osteoarthritic cartilage by coordinating cartilage matrix anabolism via effects on SOX9 PARylation." Nat Commun. 2019 Oct 25;10(1):4898.nbsp;PMID:31653858
- 3. Li N, Wang Y, et al. "Tankyrase disrupts metabolic homeostasis and promotes tumorigenesis by inhibiting LKB1-AMPK signalling." Nat Commun. 2019 Sep 25;10(1):4363.nbsp;PMID:31554794
- 4. Jia J, Qiao Y, et al. "Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade." PLoS One. 2017 Sep 6;12(9):e0184068. PMID:28877210
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 529.96 |
Cas No. | 1380672-07-0 |
Formula | C25H16ClN7O3S |
Solubility | ≥26.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | (E)-4-(5-(2-(4-(2-chlorophenyl)-5-(5-(methylsulfonyl)pyridin-2-yl)-4H-1,2,4-triazol-3-yl)vinyl)-1,3,4-oxadiazol-2-yl)benzonitrile |
SDF | Download SDF |
Canonical SMILES | CS(C1=CN=C(C2=NN=C(N2C3=CC=CC=C3Cl)/C([H])=C([H])/C(O4)=NN=C4C5=CC=C(C#N)C=C5)C=C1)(=O)=O |
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 |
COLO-320DM细胞系 |
溶解方法 |
在DMSO中的溶解度> 26.5mg/mL。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
0.2 μmol/L,7-13天 |
应用 |
G007-LK抑制细胞周期进程,降低集落形成并诱导分化,表明细胞b-catenin依赖的未分化状态的维持可能被tankyrase酶的抑制而阻断。 |
动物实验[1]: | |
动物模型 |
异种移植COLO-320DM肿瘤小鼠 |
剂量 |
20,40,60 mg/kg,腹腔注射,每天一次持续21天 |
应用 |
G007-LK对异种移植COLO-320DM肿瘤小鼠具有抗肿瘤功效。在这些小鼠中,TNKS1和TNKS2蛋白水平降低,AXIN1和AXIN2稳定,b-catenin水平降低。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1] Lau T, Chan E, Callow M, Waaler J, et. al. A novel tankyrase small-molecule inhibitor suppresses APC mutation-driven colorectal tumor growth. Cancer Res. 2013 May 15;73(10):3132-44. |
质量控制和MSDS
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