title: Allosteric inhibitors of Akt1 and Akt2: a naphthyridinone with efficacy in an A2780 tumor xenograft model.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., PO Box 4, West Point, PA 19486 USA. mark_bilodeau@merck.com
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
authors.forename: Adrienne E
authors.initials: AE
authors.lastname: Balitza
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Manley
authors.forename: Stanley F
authors.initials: SF
authors.lastname: Barnett
authors.forename: Deborah
authors.initials: D
authors.lastname: Defeo-Jones
authors.forename: Kathleen
authors.initials: K
authors.lastname: Haskell
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Jones
authors.forename: Karen
authors.initials: K
authors.lastname: Leander
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Robinson
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Smith
authors.forename: Hans E
authors.initials: HE
authors.lastname: Huber
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D004195:Disease Models, Animal; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines; D051057:Proto-Oncogene Proteins c-akt