| Identification | Back Directory | [Name]
5-(6-(3-Methoxyoxetan-3-yl)-4-Morpholinothieno[3,2-d]pyriMidin-2-yl)pyriMidin-2-aMine | [CAS]
1394076-92-6 | [Synonyms]
GNE-317
CS-1716
GNE-317;GNE 317;GNE317
5-(6-(3-Methoxyoxetan-3-yl)-4-Morpholinothieno[3,2-d]pyriMidin-2-yl)pyriMidin-2-aMine
5-(6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine
5-(6-(3-Methoxyoxetan-3-yl)-4-Morpholinothieno[3,2-d]pyriMidin-2-yl)pyriMidin-2-aMine USP/EP/BP
5-[6-(3-METHOXYOXETAN-3-YL)-7-METHYL-4-MORPHOLIN-4-YLTHIENO[3,2-D]PYRIMIDIN-2-YL]PYRIMIDIN-2-AMINE
2-Pyrimidinamine, 5-[6-(3-methoxy-3-oxetanyl)-7-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-2-yl]- | [Molecular Formula]
C18H20N6O3S | [MDL Number]
MFCD28900677 | [MOL File]
1394076-92-6.mol | [Molecular Weight]
400.455 |
| Chemical Properties | Back Directory | [storage temp. ]
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C | [solubility ]
Soluble in DMSO | [form ]
A solid | [color ]
Light yellow to khaki |
| Hazard Information | Back Directory | [Biological Activity]
gne-317 is a potent inhibitor of pi3k [1].phosphatidylinositol-4,5-bisphosphate 3-kinase (pi3k) are a series of enzymes and play an important role in cell growth, proliferation, differentiation, survival, motility and intracellular trafficking.in the gl261 cell line, gne-317 showed cytotoxic activity [2].in mouse brain, gne-317(50 mg/kg) significantly inhibited pakt, p4ebp1 and ps6 by 80%, 84%, and 92% respectively, which were downstream markers of the pi3k/mtor pathway. in u87, gs2 and gbm10 tumor-bearing mice, gne-317 inhibited tumor growth by 90%, 50% and a survival benefit, respectively [1]. in c57b6/j mice inoculated with gl261-gfp-luc cells, the concentrations of gne-317 in the normal brain, tumor core and rim were not significantly different. in tumor-bearing mice, gne-317 significantly reduced the levels of p-aktser473, p-s6ser235/236 and p-4ebp1thr37/46 within the tumor [2]. in u87 and gs2 glioblastoma multiforme (gbm) models, gne-317 was uniformly distributed in the brain. the brain-to-plasma ratios for gne-317 were greater than 1, in agreement with the brain penetration properties of gne-317 [3]. | [in vitro]
GNE-317 is not a substrate of P-gp or BCRP transporter in transfected Madin-Darby canine kidney (MDCK) cells. Binding of it to plasma proteins exhibits a free fraction of 14.9 % in mouse plasma, and binding to brain tissues is higher, with a free fraction of 5.4%.It shows cytostasis but no cell death to U87 cells. | [in vivo]
GNE-317 (40 mg/kg, po) markedly inhibits the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 (40 mg/kg, po) ) is ef?cacious in the U87 and GS2 orthotopic models, achieving tumor growth inhibition of 90% and 50%, respectively. In the GBM10 tumor model, GNE-317 (30 mg/kg, po; 40 mg/kg the ?rst 2 weeks) extends the survival of mice from a median of 55.5 to 75 days. | [target]
| PI3K | mTOR | [References]
[1]. salphati l, heffron tp, alicke b, et al. targeting the pi3k pathway in the brain--efficacy of a pi3k inhibitor optimized to cross the blood-brain barrier. clin cancer res, 2012, 18(22): 6239-6248.
[2]. becker cm, oberoi rk, mcfarren sj, et al. decreased affinity for efflux transporters increases brain penetrance and molecular targeting of a pi3k/mtor inhibitor in a mouse model of glioblastoma. neuro oncol, 2015, pii: nov081.
[3]. salphati l, shahidi-latham s, quiason c, et al. distribution of the phosphatidylinositol 3-kinase inhibitors pictilisib (gdc-0941) and gne-317 in u87 and gs2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. drug metab dispos, 2014, 42(7): 1110-1116. |
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Tags:1394076-92-6
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