Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM. Torin 1 shows over 100-fold selectivity for mTOR over PI3Kα and other PI3K-like kinases, including ATM, DNA-PK, and hVps34, as well as 450 other protein kinases. Torin 1 induces autophagy in HeLa cells. Torin 1 is efficacious at a dose of 20 mg/kg in inhibiting downstream effectors of mTOR in mice. In a recent study, it is reported Torin 1 increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway.
Peterson TR, et al. Cell. 2011 Aug 5;146(3):408-20. PMID: 21816276.
mTORC1 inhibition increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON.
Li J, et al. Am J Physiol Cell Physiol. 2011 Jul;301(1):C213-26. PMID: 21508335.
mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs.
Dowling RJ, et al. Science. 2010 May 28;328(5982):1172-6. PMID: 20508131.
An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1.
Thoreen CC, et al. J Biol Chem. 2009 Mar 20;284(12):8023-32. PMID: 19150980.
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LY303511 hydrochloride is a structural analogue of LY294002. LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors.
MHY1485 is an mTOR activator that potently inhibits autophagy by suppression of fusion between autophagosomes and lysosomes.
CZ415 is a potent ATP-competitive mTOR inhibitor with very good cell permeability.
GNE-477 is a potent and efficacious dual PI3K (IC50=4 nM)/mTOR(Ki=21 nM) inhibitor.
Zotarolimus (ABT-578) is an analogue of rapamycin, and inhibits FKBP-12 binding with IC50 of 2.8 nM.
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