| Identification | Back Directory | [Name]
GNE 477 | [CAS]
1032754-81-6 | [Synonyms]
GNE 477
CS-1884
5-(7-Methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-
5-(7-Methyl-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
5-[7-Methyl-4-(Morpholin-4-yl)-6-[(4-Methylsulfonylpiperazin-1-yl)Methyl]thieno[3,2-d]pyriMidin-2-yl]pyriMidin-2-aMine
2-Pyrimidinamine, 5-[7-methyl-6-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-
5-[7-Methyl-4-(morpholin-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine GNE 477 | [Molecular Formula]
C21H28N8O3S2 | [MDL Number]
MFCD20527726 | [MOL File]
1032754-81-6.mol | [Molecular Weight]
504.63 |
| Chemical Properties | Back Directory | [density ]
1.51±0.1 g/cm3(Predicted) | [storage temp. ]
Desiccate at -20°C | [solubility ]
insoluble in H2O; insoluble in EtOH; ≥16.69 mg/mL in DMSO with gentle warming | [form ]
Powder | [pka]
4.22±0.10(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor. | [Biological Activity]
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]. | [IC 50]
4 and 21 nmol/l for pi3k and mtor, respectively | [References]
[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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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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