GNE-617
(Synonyms: N-[[4-[(3,5-二氟苯基)磺酰基]苯基]甲基]咪唑并[1,2-A]吡啶-6-甲酰胺) 目录号 : GC16041
A potent Nampt inhibitor
Cas No.:1362154-70-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
hARPE-19 and hRPEpC cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 21.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.0032, 0.016, 0.08, 0.4, 2, and 10 µM, 3 d |
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Applications |
In rat retinal mixed cell population, cytotoxicity induced by GNE-617 is correlated with activity and potency. And human cells were more sensitive to cytotoxicity induced by GNE-617 than rat cells. |
| Animal experiment [2]: | |
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Animal models |
Female BALB/c SCID mice |
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Dosage form |
Oral administration, 5-30 mg/kg, twice daily for 5 days |
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Application |
When treated with GNE-617, a significant time-dependent decrease in NAD levels was observed in PC3 and HT-1080 xenograft tumors. In the HT-1080 xenograft model, GNE-617 decreased tumor NAD levels in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
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.
| Cas No. | 1362154-70-8 | SDF | |
| 别名 | N-[[4-[(3,5-二氟苯基)磺酰基]苯基]甲基]咪唑并[1,2-A]吡啶-6-甲酰胺 | ||
| 化学名 | N-(4-((3,5-difluorophenyl)sulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide | ||
| Canonical SMILES | FC1=CC(S(C2=CC=C(C=C2)CNC(C(C=C3)=CN4C3=NC=C4)=O)(=O)=O)=CC(F)=C1 | ||
| 分子式 | C21H15F2N3O3S | 分子量 | 427.42 |
| 溶解度 | ≥ 21.35mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3396 mL | 11.6981 mL | 23.3962 mL |
| 5 mM | 0.4679 mL | 2.3396 mL | 4.6792 mL |
| 10 mM | 0.234 mL | 1.1698 mL | 2.3396 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。