ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines
The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.
- Research Organization:
- Argonne National Laboratory (ANL)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1005831
- Journal Information:
- J. Med. Chem., Journal Name: J. Med. Chem. Journal Issue: (16) ; 08, 2009 Vol. 52; ISSN JMCMAR; ISSN 0022-2623
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin
The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors
Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
Journal Article
·
Thu Sep 30 00:00:00 EDT 2010
· ACS Med. Chem. Lett.
·
OSTI ID:1002767
The inhibition of MAPK potentiates the anti-angiogenic efficacy of mTOR inhibitors
Journal Article
·
Fri Apr 22 00:00:00 EDT 2011
· Biochemical and Biophysical Research Communications
·
OSTI ID:22204890
Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR)
Journal Article
·
Mon Jul 19 00:00:00 EDT 2010
· Bioorg. Med. Chem. Lett.
·
OSTI ID:1002525