KU-0063794

Description

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).

Uses

Ku 0063794 is a specific mammalian target of rapamycin (mTOR) inhibitor and may be used for the treatment of cancers.

Uses

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 in?human 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)

Definition

ChEBI: A member of the class of pyridopyrimidines that is an mTOR inhibitor and shows anti-tumour properties.

Biological Activity

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 .

Biochem/physiol Actions

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).

storage

Room temperature