Identification of GNE-477, a potent and efficacious dual PI3K/mTOR inhibitor

Autor:	Cristina Lewis, Nan Chi Wan, Jennafer Dotson, Janet L. Gunzner, Georgette Castanedo, Deepak Sampath, Laurent Salphati, Jim Nonomiya, John Lesnick, Susan Wong, Timothy P. Heffron, Christine Chang, Megan Berry, Shumei Wang, Simon Mathieu, Jodie Pang, Steve Sideris, Adrian Folkes, Vickie Tsui, Irina Chuckowree, Daniel P. Sutherlin, Alan G. Olivero, David A. Peterson, Bing-Yan Zhu
Rok vydání:	2010
Předmět:	Morpholino Clinical Biochemistry Pharmaceutical Science Thiophenes Protein Serine-Threonine Kinases Pharmacology Biochemistry Mice Dogs In vivo Drug Discovery Animals Enzyme Inhibitors Molecular Biology PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Chemistry Kinase TOR Serine-Threonine Kinases Organic Chemistry Intracellular Signaling Peptides and Proteins Discovery and development of mTOR inhibitors Small molecule Rats Pyrimidines Molecular Medicine Female
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:2408-2411
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2010.03.046
Popis:	Efforts to identify potent small molecule inhibitors of PI3 kinase and mTOR led to the discovery of the exceptionally potent 6-aryl morpholino thienopyrimidine 6. In an effort to reduce the melting point in analogs of 6, the thienopyrimidine was modified by the addition of a methyl group to disrupt planarity. This modification resulted in a general improvement in in vivo clearance. This discovery led to the identification of GNE-477 (8), a potent and efficacious dual PI3K/mTOR inhibitor.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07054715432864ef6433675ccce8e7b4 https://doi.org/10.1016/j.bmcl.2010.03.046 Zobrazit plný text záznamu Full Text from ScienceDirect