GNE-477 |
Catalog No.GC10340 |
dual PI3K/mTOR inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1032754-81-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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. |
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.
Cas No. | 1032754-81-6 | SDF | |
Chemical Name | 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 | ||
Formula | C21H28N8O3S2 | M.Wt | 504.63 |
Solubility | ≥ 16.69mg/mL in DMSO with gentle warming | Storage | Desiccate at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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