GNE-493

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性双泛 PI3K/mTOR 抑制剂，对 PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ/mTOR 的 IC50 为 3.4/12/16/16/32 nM。

A potent, selective dual pan-PI3K/mTOR inhibitor with IC50 of 3.4/12/16/16/32 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ/mTOR; displays 100-fold selective for PI3Kα over Aurora A, MLK1, Syk; has good PK profiles, and are efficacious in xenograft models; orally available.

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).

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.

GNE493 | GNE 493

PI3K/Akt/mTOR signaling

PI3K

PI3K

Cancer

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1033735-94-2

372.4447

C17H20N6O2S

>98% (HPLC)

DMSO: ≥ 45 mg/mL

CC(O)(C1=CC2=NC(C3=CN=C(N)N=C3)=NC(N4CCOCC4)=C2S1)C

Thieno[3,2-d]pyrimidine-6-methanol, 2-(2-amino-5-pyrimidinyl)-α,α-dimethyl-4-(4-morpholinyl)-

(-20℃)

With Ice Pack

≥ 2 years