title: Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity.
abstract: HTS screening identified 1 with micromolar inhibitory activity against PDK1. Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity against PDK1 and excellent selectivity against PKA.
authors.affiliation: Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA.
authors.forename: Imadul
authors.initials: I
authors.lastname: Islam
authors.forename: Judi
authors.initials: J
authors.lastname: Bryant
authors.forename: Yuo-Ling
authors.initials: YL
authors.lastname: Chou
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Kochanny
authors.forename: Wheeseong
authors.initials: W
authors.lastname: Lee
authors.forename: Gary B
authors.initials: GB
authors.lastname: Phillips
authors.forename: Hongyi
authors.initials: H
authors.lastname: Yu
authors.forename: Marc
authors.initials: M
authors.lastname: Adler
authors.forename: Marc
authors.initials: M
authors.lastname: Whitlow
authors.forename: Elena
authors.initials: E
authors.lastname: Ho
authors.forename: Dao
authors.initials: D
authors.lastname: Lentz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Polokoff
authors.forename: Babu
authors.initials: B
authors.lastname: Subramanyam
authors.forename: James M
authors.initials: JM
authors.lastname: Wu
authors.forename: Daguang
authors.initials: D
authors.lastname: Zhu
authors.forename: Richard I
authors.initials: RI
authors.lastname: Feldman
authors.forename: Damian O
authors.initials: DO
authors.lastname: Arnaiz
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D015195:Drug Design; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases