938440-64-3 Usage
Description
KU-0063794 is a cell-permeable, selective dual inhibitor of mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, with an IC50 of 10 nM. It is a member of the pyridopyrimidines class and exhibits anti-tumour properties. KU-0063794 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, without inducing apoptosis, and demonstrates efficacy in inhibiting tumor growth in a xenograft model of renal cell carcinoma.
Used in Pharmaceutical Industry:
KU-0063794 is used as a specific mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancers. It has the potential to be employed in cancer therapy by targeting the mTOR pathway, which plays a crucial role in cell growth, proliferation, and survival.
Used in Research Applications:
KU-0063794 is used as a research tool 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). This helps researchers understand the role of mTOR in various cellular processes and its potential as a therapeutic target.
Used in Metabolic Flux Analysis:
KU-0063794 is used as an mTOR inhibitor to treat effector memory (EM) CD8+ T cells for metabolic flux analysis. This application aids in understanding the metabolic changes that occur in T cells upon mTOR inhibition, which can be crucial for developing immunotherapies and other treatments.
Used in Autophagy Research:
KU-0063794 is used 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). This application helps researchers investigate the mechanisms of autophagy induction and its implications in various diseases and conditions.
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).
Check Digit Verification of cas no
The CAS Registry Mumber 938440-64-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,3,8,4,4 and 0 respectively; the second part has 2 digits, 6 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 938440-64:
(8*9)+(7*3)+(6*8)+(5*4)+(4*4)+(3*0)+(2*6)+(1*4)=193
193 % 10 = 3
So 938440-64-3 is a valid CAS Registry Number.
InChI:InChI=1/C25H31N5O4/c1-16-13-30(14-17(2)34-16)25-27-23-20(24(28-25)29-8-10-33-11-9-29)5-6-21(26-23)18-4-7-22(32-3)19(12-18)15-31/h4-7,12,16-17,31H,8-11,13-15H2,1-3H3/t16-,17+
938440-64-3Relevant articles and documents
Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014
Pike, Kurt G.,Malagu, Karine,Hummersone, Marc G.,Menear, Keith A.,Duggan, Heather M.E.,Gomez, Sylvie,Martin, Niall M.B.,Ruston, Linette,Pass, Sarah L.,Pass, Martin
, p. 1212 - 1216 (2013/03/14)
The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
