Allosteric inhibitors of Akt1 and Akt2: A naphthyridinone with efficacy in an A2780 tumor xenograft model

A series of naphthyridine and naphthyridinone allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been optimized to have potent dual activity against the activated kinase as well as the activation of Akt in cells. One molecule in particular, compound 17, has potent inh...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2008-06, Vol.18 (11), p.3178-3182
Hauptverfasser:	Bilodeau, Mark T., Balitza, Adrienne E., Hoffman, Jacob M., Manley, Peter J., Barnett, Stanley F., Defeo-Jones, Deborah, Haskell, Kathleen, Jones, Raymond E., Leander, Karen, Robinson, Ronald G., Smith, Anthony M., Huber, Hans E., Hartman, George D.
Format:	Artikel
Sprache:	eng
Schlagworte:	Akt Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Combinatorial Chemistry Techniques Disease Models, Animal Drug Design Drug Screening Assays, Antitumor Humans Mice Naphthyridines - chemical synthesis Naphthyridines - chemistry Naphthyridines - pharmacology Oncology Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Structure-Activity Relationship
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Zusammenfassung:	A series of naphthyridine and naphthyridinone allosteric dual inhibitors of Akt1 and 2 have been developed. These compounds have been optimized to have potent dual activity against the activated kinase as well as the activation of Akt in cells. One molecule in particular, compound 17, has potent inhibitory activity against Akt1 and 2 in vivo in a mouse lung and efficacy in a tumor xenograft model.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2008.04.074