GNE-493

Cas No.:	1033735-94-2
Chemical Name:	2-(2-(2-aminopyrimidin-5-yl)-4-morpholinothieno[3,2-d]pyrimidin-6-yl)propan-2-ol
Synonyms:	GNE 493，GNE493
SMILES:	OC(C)(C)C1=CC2=C(S1)C(N3CCOCC3)=NC(C4=CN=C(N)N=C4)=N2
Formula:	C17H20N6O2S
M.Wt:	372.44
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	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].
In Vitro:	GNE-493 is a low molecular weight, potent dual inhibitor of pan-PI3 kinases and mTOR. GNE-493 displays approximately equipotent inhibition of Class I PI3K isoforms, is submitted for screening in a 142 kinase panel provided by Invitrogen’s SelectScreen service. Of these kinases, only three are subject to greater than 50% inhibition by GNE-493, and none are inhibited greater than 80% when tested at 1 μM. Subsequently measured IC50s demonstrated that GNE-493 is more than 100-fold selective for PI3Kα over these three unrelated kinases (Aurora A IC50>10 μM, MLK1 IC50=591 nM and SYK IC50=371 nM)[1].