Description
Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM; exhibits 1000-fold selectivity for mTOR than PI3K.
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Molecular Formula
C35H28F3N5O2
Chemical Name
Benzo[h]-1,6-naphthyridin-2(1H)-one, 1-[4-[4-(1-oxopropyl)-1-piperazinyl]-3-(trifluoromethyl)phenyl]-9-(3-quinolinyl)-
Solubility
DMSO 2 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases.Torin1 causes cell cycle arrest through a rapamycin-resistant mechanism that is also independent of mTORC2. Torin1 disrupts mTORC1-dependent phenotypes more completely than rapamycin. Rapamycin-resistant functions of mTORC1 are required for cap-dependent translation. In a recent study, it is reported Torin1 increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON.
In vivo
Torin1 is efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrates good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues.
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