GNE-617
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.
GNE-617是一种有效的竞争性烟酰胺磷酸核糖转移酶(NAMPT)抑制剂,IC50值为5 nM [1]。
GNE-617是一种有效的NAMPT抑制剂。在NAPRT1缺陷和NAPRT1成熟细胞系中,GNE-617均可降低NAD水平,达到95% 以上,EC50值范围为0.54 nM到4.69 nM。
体外ADME实验中,GNE-617表现出最理想的体外代谢稳定性、MDCK渗透性和蛋白结合性。除此之外,GNE-617对各种细胞系具有有效的抗增殖效应。在U251、HT1080、PC3、MiaPaCa2 和HCT116 细胞系中的IC50值分别为1.8 nM、2.1 nM、2.7 nM、7.4 nM和2 nM。而且,在U251人胶质母细胞瘤异种移植小鼠模型中,GNE-617具有显著的抗肿瘤效应,且对体重减轻无明显影响[1,2]。
参考文献:
[1] Zheng X, Bauer P, Baumeister T, et al. Structure-based discovery of novel amide-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors. Journal of medicinal chemistry, 2013, 56(16): 6413-6433.
[2] O'Brien T, Oeh J, Xiao Y, et al. Supplementation of Nicotinic Acid with NAMPT Inhibitors Results in Loss of In Vivo Efficacy in NAPRT1-Deficient Tumor Models. Neoplasia, 2013, 15(12): 1314-IN3.
- 1. Maximilian Clausing, DoreenWilliam, et al. "Different Effects of RNAi-Mediated Downregulation or Chemical Inhibition of NAMPT in an Isogenic IDH Mutant and Wild-Type Glioma Cell Model." Int J Mol Sci. 2022 May 21;23(10):5787. PMID: 35628596
- 2. Xian-Pei Heng, Zhi-Ta Wang, et al. "Mechanisms of Dangua Recipe in Improving Glycolipid Metabolic Disorders Based on Transcriptomics." Chin J Integr Med. 2022 Feb;28(2):130-137. PMID: 34755288
Storage | Store at -20°C |
M.Wt | 427.42 |
Cas No. | 1362154-70-8 |
Formula | C21H15F2N3O3S |
Solubility | ≥21.35 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | N-(4-((3,5-difluorophenyl)sulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide |
SDF | Download SDF |
Canonical SMILES | FC1=CC(S(C2=CC=C(C=C2)CNC(C(C=C3)=CN4C3=NC=C4)=O)(=O)=O)=CC(F)=C1 |
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 |
hARPE-19和hRPEpC细胞系 |
溶解方法 |
在DMSO中的溶解度大于21.4 mg/mL。为了获得更高的浓度,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 |
0.0032,0.016,0.08,0.4,2和10 μM,3 d |
应用 |
在大鼠视网膜混合细胞群中,GNE-617诱导的细胞毒性与其效价和活性相关。和大鼠细胞相比,人的细胞对GNE-617诱导的细胞毒性更加敏感。 |
动物实验[2]: | |
动物模型 |
雌性BALB/c SCID小鼠 |
剂量 |
口服给药,5-30 mg/kg,每天两次持续5天 |
应用 |
GNE-617给药后,在PC3和HT-1080异种移植瘤中NAD的水平随着时间的增加显著减少。在HT-1080异种移植瘤模型中,GNE-617以剂量依赖的方式减少肿瘤中NAD的水平。 |
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]. Zabka T S, Singh J T, Dhawan P, et al. Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase[J]. Toxicological Sciences, 2014: kfu268. [2]. O'Brien T, Oeh J, Xiao Y, et al. Supplementation of nicotinic acid with NAMPT inhibitors results in loss of in vivo efficacy in NAPRT1-deficient tumor models[J]. Neoplasia, 2013, 15(12): 1314IN1-1329IN3. |
质量控制和MSDS
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