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ChemicalBook--->CAS DataBase List--->1033735-94-2

1033735-94-2

1033735-94-2 Structure

1033735-94-2 Structure
IdentificationBack Directory
[Name]

GNE-493
[CAS]

1033735-94-2
[Synonyms]

CS-1783
GNE-493
GNE 493;GNE493
2-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol
2-[2-(2-aminopyrimidin-5-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]propan-2-ol
Thieno[3,2-d]pyrimidine-6-methanol, 2-(2-amino-5-pyrimidinyl)-α,α-dimethyl-4-(4-morpholinyl)-
2-(2-Amino-5-pyrimidinyl)-alpha,alpha-dimethyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-methanol
2-(2-Amino-5-pyrimidinyl)-alpha,alpha-dimethyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine-6-methanol GNE-493
[Molecular Formula]

C17H20N6O2S
[MDL Number]

MFCD18251526
[MOL File]

1033735-94-2.mol
[Molecular Weight]

372.44
Chemical PropertiesBack Directory
[density ]

1.408±0.06 g/cm3(Predicted)
[storage temp. ]

Desiccate at -20°C
[solubility ]

DMF:20.0(Max Conc. mg/mL);53.7(Max Conc. mM)
DMF:PBS (pH 7.2) (1:1):0.5(Max Conc. mg/mL);1.34(Max Conc. mM)
DMSO:45.0(Max Conc. mg/mL);120.82(Max Conc. mM)
Ethanol:1.1(Max Conc. mg/mL);2.95(Max Conc. mM)
[form ]

Powder
[pka]

13.17±0.29(Predicted)
[color ]

Off-white to gray
Hazard InformationBack Directory
[Uses]

GNE-493 is a potent, selective, and orally available dual pan-PI3-kinase/mTOR inhibitor with IC50s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR.
[in vivo]

To confirm and compare in vivo efficacy, GNE-493 is examined in the human MCF7.1 breast cancer xenograft model that harbors a PI3Kα activating mutation. Mice bearing xenografts are dosed orally once daily with 10 mg/kg of GNE-493 for 21 continuous days. Similar to observations made in the PC3 prostate cancer xenograft model, 10 mg/kg of GNE-493 results in 73% tumor growth inhibition at day 21 when compared to vehicle control animals. When achieving comparable levels of drug exposure, GNE-493 shows a similar suppression of the PI3K pathway and consequently, a similar efficacy profile against MCF7.1 breast tumors[1].

[IC 50]

PI3Kα: 3.4 nM (IC50); PI3Kβ: 12 nM (IC50); PI3Kδ: 16 nM (IC50); PI3Kγ: 16 nM (IC50); mTOR: 30 nM (IC50)
[storage]

Desiccate at -20°C
[References]

[1] Sutherlin DP, et al. Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. J Med Chem. 2010 Feb 11;53(3):1086-97. DOI:10.1021/jm901284w
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