Discovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a Potent, Selective, and Orally Available …
Journal of medicinal chemistry, 2011•ACS Publications
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 …
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 …
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.
ACS Publications