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GNE-617

现货
Catalog No.
B1271
NAMPT 抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 3,300.00
现货
2mg
¥ 1,580.00
现货
5mg
¥ 2,520.00
现货
10mg
¥ 3,960.00
现货
50mg
¥ 10,040.00
现货
100mg
¥ 15,620.00
现货

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Background

GNE-617 is a potent and competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with IC50 value of 5nM [1].

GNE-617 is a potent inhibitor of NAMPT. It reduces the NAD levels in a > 95% reduction in both NAPRT1-deficient and NAPRT1-proficient cell lines and exerts EC50 values ranging from 0.54nM to 4.69nM. In the invitro ADME assessments, GNE-617 shows the most optimal combination of in vitro metabolic stability, MDCK permeability and protein binding. Besides that, GNE-617 has potent antiproliferation effects on various cell lines. The IC50 values of it in U251, HT1080, PC3, MiaPaCa2 and HCT116 cell lines are 1.8nM, 2.1nM, 2.7nM, 7.4nM and 2nM, respectively. Moreover, GNE-617 also shows significant antitumor effects on U251 human glioblastoma tumor xenografts in mice and has no obvious effect on body weight loss [1, 2].

References:
[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.

Chemical Properties

StorageStore at -20°C
M.Wt427.42
Cas No.1362154-70-8
FormulaC21H15F2N3O3S
Solubility≥21.35mg/mL in DMSO
Chemical NameN-(4-((3,5-difluorophenyl)sulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide
SDFDownload SDF
Canonical SMILESFC1=CC(S(C2=CC=C(C=C2)CNC(C(C=C3)=CN4C3=NC=C4)=O)(=O)=O)=CC(F)=C1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

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

化学结构

GNE-617