GNE-477dual PI3K/mTOR inhibitor CAS# 1032754-81-6 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1032754-81-6 | SDF | Download SDF |
| PubChem ID | 25207689 | Appearance | Powder |
| Formula | C21H28N8O3S2 | M.Wt | 504.63 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 16.67 mg/mL (33.03 mM; Need ultrasonic) | ||
| Chemical Name | 5-[7-methyl-6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine | ||
| SMILES | CC1=C(SC2=C1N=C(N=C2N3CCOCC3)C4=CN=C(N=C4)N)CN5CCN(CC5)S(=O)(=O)C | ||
| Standard InChIKey | AKKCGLXULFRAET-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H28N8O3S2/c1-14-16(13-27-3-5-29(6-4-27)34(2,30)31)33-18-17(14)25-19(15-11-23-21(22)24-12-15)26-20(18)28-7-9-32-10-8-28/h11-12H,3-10,13H2,1-2H3,(H2,22,23,24) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor.In Vitro:GNE-477 (Compound 8) has improved potency in the MCF7.1 cell proliferation assay with an EC50 of 143 nM[1].In Vivo:GNE-477 also exhibits stasis in a PC3 tumor growth inhibition study. In an experiment evaluating the tumor growth inhibition of a PC3 tumor xenograft over 14 days, stasis is achieved at a 20 mg/kg QD dose and significant inhibition is observed with doses as low as 1 mg/kg QD. GNE-477 is generally well tolerated during this study as demonstrated by acceptable levels of weight loss comparable to that observed with the animals in the vehicle cohort[1]. References: | |||||
GNE-477 Dilution Calculator
GNE-477 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.9816 mL | 9.9082 mL | 19.8165 mL | 39.633 mL | 49.5412 mL |
| 5 mM | 0.3963 mL | 1.9816 mL | 3.9633 mL | 7.9266 mL | 9.9082 mL |
| 10 mM | 0.1982 mL | 0.9908 mL | 1.9816 mL | 3.9633 mL | 4.9541 mL |
| 50 mM | 0.0396 mL | 0.1982 mL | 0.3963 mL | 0.7927 mL | 0.9908 mL |
| 100 mM | 0.0198 mL | 0.0991 mL | 0.1982 mL | 0.3963 mL | 0.4954 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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.
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Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor.[Pubmed:20346656]
Bioorg Med Chem Lett. 2010 Apr 15;20(8):2408-11.
Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.
