Abstract
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.
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Combinatorial Chemistry Techniques
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Disease Models, Animal
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Drug Design
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Drug Screening Assays, Antitumor
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Humans
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Mice
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Naphthyridines / chemical synthesis*
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Naphthyridines / chemistry
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Naphthyridines / pharmacology*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
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Proto-Oncogene Proteins c-akt / metabolism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Naphthyridines
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Proto-Oncogene Proteins c-akt