title: Design and synthesis of novel amide AKT1 inhibitors with selectivity over CDK2.
abstract: Through the analysis of X-ray crystallographic information and previous SAR studies, a novel series of protein kinase B (PKB/AKT) inhibitors was developed. The compounds showed nanomolar inhibition of AKT1 and were selective against cyclin-dependent kinase 2 (CDK2).
authors.affiliation: Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. katea@amgen.com
authors.forename: Kate S
authors.initials: KS
authors.lastname: Ashton
authors.forename: David J
authors.initials: DJ
authors.lastname: St Jean
authors.forename: Steve F
authors.initials: SF
authors.lastname: Poon
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lee
authors.forename: John G
authors.initials: JG
authors.lastname: Allen
authors.forename: Shiwen
authors.initials: S
authors.lastname: Zhang
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lofgren
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Christopher
authors.initials: C
authors.lastname: Fotsch
authors.forename: Randall
authors.initials: R
authors.lastname: Hungate
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051357:Cyclin-Dependent Kinase 2