title: Modifications of the GSK3beta substrate sequence to produce substrate-mimetic inhibitors of Akt as potential anti-cancer therapeutics.
abstract: Amplification, overexpression, and elevated activation of Akt have been detected in many human malignancies making it an important target for cancer therapy. The Akt substrate-binding site offers a large number of potential interactions to an appropriately designed small molecule and can form the basis for the development of selective inhibitors. Here, we report the progression of GSK3beta substrate-mimetic inhibitors towards the development of a potent, small molecule substrate-mimetic inhibitor of Akt.
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Kayser
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Glenn
authors.forename: Said M
authors.initials: SM
authors.lastname: Sebti
authors.forename: Jin Q
authors.initials: JQ
authors.lastname: Cheng
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008956:Models, Chemical; D009369:Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010455:Peptides; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3