1266690-03-2Relevant academic research and scientific papers
Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[ h ][1,6]naphthyridin-2(1 H)-one (torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer
Liu, Qingsong,Wang, Jinhua,Kang, Seong A.,Thoreen, Carson C.,Hur, Wooyoung,Ahmed, Tausif,Sabatini, David M.,Gray, Nathanael S.
, p. 1473 - 1480 (2011/05/05)
The mTOR mediated PI3K/AKT/mTOR signal transduction pathway has been demonstrated to play a key role in a broad spectrum of cancers. Starting from the mTOR selective inhibitor 1 (Torin1), a focused medicinal chemistry effort led to the discovery of an improved mTOR inhibitor 3 (Torin2), which possesses an EC50 of 0.25 nM for inhibiting cellular mTOR activity. Compound 3 exhibited 800-fold selectivity over PI3K (EC50: 200 nM) and over 100-fold binding selectivity relative to 440 other protein kinases. Compound 3 has significantly improved bioavailability (54%), metabolic stability, and plasma exposure relative to compound 1.
