The mammalian target of rapamycin (mTOR) is a serine-threonine kinase which acts as part of two distinct complexes, TORC1 and TORC2. Both complexes (TORC1/2) play central roles in cell growth, gene expression, angiogenesis, and cell survival. Ku-0063794 is a cell-permeable, selective dual inhibitor of mTORC1 and mTORC2 (IC50 = 10 nM). It does not affect the activity of 76 other protein kinases or seven lipid kinases, including PI3Ks. Ku-0063794 inhibits cell growth by inducing G1-cell cycle arrest and autophagy, but not apoptosis, and inhibits tumor growth in a xenograft model of renal cell carcinoma (8 mg/kg for 46 days).
Ku 0063794 is a specific mammalian target of rapamycin (mTOR) inhibitor and may be used for the treatment of cancers.
KU 0063794 has been used:
- as a mammalian target of rapamycin (mTOR) inhibitor to study the effects of follicular stimulating hormone (FSH) in mTOR phosphorylation and vascular cell adhesion molecule-1 (VCAM-1) expression inhuman umbilical vascular endothelial cells (HUVECs)
- as a mTOR inhibitor to treat effector memory (EM) CD8+ T cells for metabolic flux analysis
- as an autophagy inducer to demonstrate the utility of p62 and LC3B-II quantification in HEK293T cells and primary cultures of rat neurons and astrocytes using time-resolved fluorescence resonance energy transfer (TR-FRET)
ChEBI: A member of the class of pyridopyrimidines that is an mTOR inhibitor and shows anti-tumour properties.
Selective inhibitor of mammalian target of rapamycin (mTOR) (IC 50 ~10 nM for mTORC1 and mTORC2 respectively). Displays no activity at PI 3-kinase or 76 other kinases tested. Inhibits activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK. Suppresses cell growth and induces G 1 cell cycle arrest in vitro .
KU 0063794 induces autophagy. It is cell-permeant and suppresses activation and hydrophobic motif phosphorylation of protein kinase B (Akt), p70 ribosomal S6 kinase (S6K) and serum and glucocorticoid protein kinase (SGK).
[1] JUAN M GARCíA-MARTíNEZ. Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR).[J]. Biochemical Journal, 2009, 421 1: 29-42. DOI:
10.1042/bj20090489[2] SHI-JIANG FEI. Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells.[J]. PLoS ONE, 2013: e69104. DOI:
10.1371/journal.pone.0069104[3] HAO ZHANG. A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models.[J]. PLoS ONE, 2013: e54918. DOI:
10.1371/journal.pone.0054918
