Cell lines

MEFs

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

4 days; 1-6 h

Applications

250 nM Torin1 fully inhibits cell proliferation and induces a G1/S cell cycle arrest. Furthermore, 250 nM Torin1 decreases cell size to a larger degree than 50 nM rapamycin. In addtion, Torin1 disrupts mTORC1-dependent phenotypes more Completely than rapamycin.

Animal models

U87-MG glioblastoma mice xenografts

Dosage form

Once daily IP dosing of 20 mg/kg

Preparation method

Dissolved at 25 mg/mL in 100% N-methyl-2-pyrrolidone

Applications

Torin1 treatment for 10 consecutive days leads to a greater than 99% inhibition of tumor growth. The tumor continues to grow after halt of the treatment, indicating that Torin1 is primarily cytostatic and that a substantial number of tumor cells are still viable during treatment.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Torin 1, a tricyclic benzonaphthyridinone, is a potent and selective inhibitor of the mammalian target of rapamycin (mTOR) kinase, which is the catalytic subunit of two functionally distinct complexes and plays a pivotal role in the regulation of cell growth, proliferation and survival. Torin 1 directly inhibits the two mTOR-containing complexes, mTORC1 and mTORC2, through an ATP-competitive mechanism with half maximal inhibitory concentration IC50 of 2 nM and 10 nM respectively. Torin 1 has been found to impair cell growth and proliferation through a mechanism involving mTORC1 inhibition other than mTORC2 inhibition, in which the rapamycin-resistant functions of mTORC1 is suppressed.

References:
[1]Thoreen CC1, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009 Mar 20;284(12):8023-32. doi: 10.1074/jbc.M900301200. Epub 2009 Jan 15.
[2]Liu Q1, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS. Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. J Med Chem. 2010 Oct 14;53(19):7146-55. doi: 10.1021/jm101144f.