Background
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).
Molecular Formula
C24H15F3N4O
Molecular Weight
432.4 g/mol
Purity
>98%
CAS
1223001-51-1
Solubility
Soluble in DMSO at 8mg/ml.
Storage
Directions for Use
Torin 2 is supplied as a lyophilized powder. For a 5 mM stock, reconstitute the 5 mg in 2.31 ml DMSO. First add 1 ml DMSO to the tube containing the chemical, vortex, and dispense into a new, larger tube. Repeat this action to transfer any residual material. Add additional DMSO to the new tube to bring the volume up to 2.31 ml. Heating to 37ºC and/or additional vortexing may be required.
Working concentrations and length of treatment can vary depending on the desired effect, but it is typically used at 10-1,000 nM for 1-24 hr.
Background References
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
Trademarks and Patents
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