GNE-493 is a potent, selective, and orally available dualpan-PI3-kinase/mTORinhibitor withIC₅₀s of 3.4 nM, 12 nM, 16 nM, 16 nM and 32 nM forPI3Kα,PI3Kβ,PI3Kδ,PI3KγandmTOR.

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].

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].

372.44

Solid

C₁₇H₂₀N₆O₂S

1033735-94-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 45 mg/mL(120.82 mM)

*"≥" means soluble, but saturation unknown.

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