title: Thieno[3,2-d]pyrimidin-4(3H)-one derivatives as PDK1 inhibitors discovered by fragment-based screening.
abstract: Ligand efficient fragments binding to PDK1 were identified by an NMR fragment-based screening approach. Computational modeling of the fragments bound to the active site led to the design and synthesis of a series of novel 6,7-disubstituted thienopyrimidin-4-one compounds, with low micromolar inhibitory activity against PDK1 in a biochemical enzyme assay.
authors.affiliation: S*BIO PTE LTD, 1 Science Park Road, #05-09 The Capricorn, Singapore Science Park II, Singapore 117528, Singapore.
authors.forename: Angeline C-H
authors.initials: AC
authors.lastname: Lee
authors.forename: Pondy Murugappan
authors.initials: PM
authors.lastname: Ramanujulu
authors.forename: Anders
authors.initials: A
authors.lastname: Poulsen
authors.forename: Meredith
authors.initials: M
authors.lastname: Williams
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Blanchard
authors.forename: Diana M
authors.initials: DM
authors.lastname: Ma
authors.forename: Zahid
authors.initials: Z
authors.lastname: Bonday
authors.forename: Kay Lin
authors.initials: KL
authors.lastname: Goh
authors.forename: Kee Chuan
authors.initials: KC
authors.lastname: Goh
authors.forename: Miah Kiat
authors.initials: MK
authors.lastname: Goh
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wood
authors.forename: Brian W
authors.initials: BW
authors.lastname: Dymock
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; C578564:Pdpk1 protein, mouse; D017346:Protein Serine-Threonine Kinases