GNE-477
目录号 : GC10340
A dual PI3K and mTOR inhibitor
Cas No.:1032754-81-6
Sample solution is provided at 25 µL, 10mM.
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IC50: 4 and 21 nmol/L for PI3K and mTOR, respectively
GNE-477 is a potent dual PI3K/mTOR inhibitor. Owing to the common association with oncogenic malignancies, the PI3K/AKT/mTOR signaling pathway is regarded as an attractive area of research for the identification of oral small molecule inhibitors.
In vitro: GNE-477 was found to inhibit PI3K-α, β, δ, and γ with IC50s of 4, 86, 6, and 15 nM, respectively. [1].
In vivo: A direct comparison of GNE-477 with its des-methyl analog revealed that the trend of reduced in vivo clearance in rats is also observed in dogs and mice. The clearance improvement was significant in dogs where the des-methyl analog was cleared at two-thirds the rate of hepatic blood flow while GNE-477 had low clearance. In an study evaluating the tumor growth inhibition of a PC3 tumor xenograft10 over 14 days, stasis was achieved at a 20 mg/kg QD dose of GNE-477 and significant inhibition was found with doses as low as 1 mg/kg QD. GNE-477 was generally well tolerated during this study as shown by acceptable levels of weight loss comparable to that in the vehicle cohort [1].
Clinical trial: N/A
Reference:
[1] Heffron TP,Berry M,Castanedo G,Chang C,Chuckowree I,Dotson J,Folkes A,Gunzner J,Lesnick JD,Lewis C,Mathieu S,Nonomiya J,Olivero A,Pang J,Peterson D,Salphati L,Sampath D,Sideris S,Sutherlin DP,Tsui V,Wan NC,Wang S,Wong S,Zhu BY. Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor. Bioorg Med Chem Lett.2010 Apr 15;20(8):2408-11.
Animal experiment: | Mice, Rats and Dogs[1]Female nu/nu mice are dosed with the GNE-477 HCl salt as a solution intraveinously (1 mg/kg) in 5% DMSO/5% cremophor and dosed orally as a solution in 80% PEG (5 mg/kg). Male rats are dosed with the GNE-477 TFA salt as a solution intraveinously (1 mg/kg) in 5% DMSO/5% cremophor and dosed orally as a solution in 80% PEG (5 mg/kg). Male beagle dogs are dosed with the GNE-477 HCl salt as a solution intraveinously (1 mg/kg) in 10% HP-β-CD and dosed orally as a suspension in MCT (2 mg/kg). Efficacy study of GNE-477 in the PC3-NCI tumor xenograft model is proformed. The percent of tumor growth inhibition (TGI) at the end of study (day 14) is measured and compared with the vehicle control group. |
References: [1]. Heffron TP, et al. Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2408-11. | |
| Cas No. | 1032754-81-6 | SDF | |
| 化学名 | 5-(7-methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine | ||
| Canonical SMILES | O=S(N1CCN(CC2=C(C)C3=NC(C4=CN=C(N)N=C4)=NC(N5CCOCC5)=C3S2)CC1)(C)=O | ||
| 分子式 | C21H28N8O3S2 | 分子量 | 504.63 |
| 溶解度 | ≥ 16.69mg/mL in DMSO with gentle warming | 储存条件 | Desiccate 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9816 mL | 9.9082 mL | 19.8165 mL |
| 5 mM | 0.3963 mL | 1.9816 mL | 3.9633 mL |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9816 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet