Name | 5-[7-methyl-6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine |
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Synonyms |
2-Pyrimidinamine, 5-[7-methyl-6-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-
unii-0e8la9h0ry 5-[7-Methyl-6-{[4-(methylsulfonyl)-1-piperazinyl]methyl}-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-2-yl]-2-pyrimidinamine gne-477 |
Description | GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor. |
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Related Catalog | |
Target |
PI3Kα:4 nM (IC50) mTOR:21 nM (Ki) |
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]. |
Animal Admin | 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 |
Density | 1.5±0.1 g/cm3 |
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Boiling Point | 693.6±65.0 °C at 760 mmHg |
Molecular Formula | C21H28N8O3S2 |
Molecular Weight | 504.629 |
Flash Point | 373.3±34.3 °C |
Exact Mass | 504.172577 |
PSA | 168.02000 |
LogP | 1.00 |
Vapour Pressure | 0.0±2.2 mmHg at 25°C |
Index of Refraction | 1.717 |
Storage condition | 2-8℃ |