Torin 2 #14385

Torin 2 is a potent and selective ATP-competitive mTOR inhibitor with superior pharmacokinetics over the Torin 1 predecessor (1,2). A series of in vitro kinase activity assays indicate that Torin 2 inhibits mTORC1 with an IC₅₀ of 2.1 nM. Cellular activity assays demonstrate that Torin 2 inhibits cellular mTOR activity with an EC₅₀ of 0.25 nM. These assays also indicate that Torin 2 has an 800-fold selectivity over P13K (EC₅₀ of 200 nM) and a over 800-fold selectivity over 400 other protein kinases (2). Unlike Torin 1, Torin 2 inhibits the phosphatidylinositol-3 kinase–like kinase (PIKK) family members ATM (EC₅₀ = 25 nM), ATR (EC₅₀ = 35 nM), and DNA-PK (IC₅₀ = 118 nM) (2). Investigators demonstrate that Torin 2 treatment of cells attenuates phosphorylation of mTOR downstream targets, inhibits cell proliferation of several cancer cell types, and induces apoptosis and autophagy (2,3). Indirect activation and nuclear translocation of TFEB (EC₅₀ = ~1.6 nM) through Torin 2 inhibition of mTORC1 has also been observed (4).