Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors

Autor:	Stanley F. Barnett, Zhijian Zhao, Joel R. Huff, Deborah Defeo-Jones, Raymond E. Jones, Craig W. Lindsley, Mark E. Duggan, William H. Leister, Ronald G. Robinson, Hans E. Huber, George D. Hartman
Rok vydání:	2005
Předmět:	Clinical Biochemistry Allosteric regulation Pharmaceutical Science AKT1 Apoptosis AKT2 Protein Serine-Threonine Kinases Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship Allosteric Regulation Proto-Oncogene Proteins Quinoxalines Drug Discovery Humans Enzyme Inhibitors Phosphorylation Protein kinase A Molecular Biology Protein kinase B biology Chemistry Organic Chemistry Isoenzymes Enzyme inhibitor embryonic structures biology.protein Molecular Medicine Signal transduction Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 15:761-764
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2004.11.011
Popis:	This letter describes the development of two series of potent and selective allosteric Akt kinase inhibitors that display an unprecedented level of selectivity for either Akt1, Akt2 or both Akt1/Akt2. An iterative analog library synthesis approach quickly provided a highly selective Akt1/Akt2 inhibitor that induces apoptosis in tumor cells and inhibits Akt phosphorylation in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb2fa3cb99fd80ce08bf7036b95fb412 https://doi.org/10.1016/j.bmcl.2004.11.011 Zobrazit plný text záznamu Full Text from ScienceDirect