title: Identification of inhibitors of protein kinase B using fragment-based lead discovery.
abstract: Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80 microM) was identified as a novel, low molecular weight inhibitor of protein kinase B (PKB). Herein we describe the rapid elaboration of highly potent and ligand efficient analogues using a fragment growing approach. Iterative structure-based design was supported by protein-ligand structure determinations using a PKA-PKB "chimera" and a final protein-ligand structure of a lead compound in PKBbeta itself.
authors: Gordon
authors: G
authors: Saxty
authors: Steven J
authors: SJ
authors: Woodhead
authors: Valerio
authors: V
authors: Berdini
authors: Thomas G
authors: TG
authors: Davies
authors: Marcel L
authors: ML
authors: Verdonk
authors: Paul G
authors: PG
authors: Wyatt
authors: Robert G
authors: RG
authors: Boyle
authors: David
authors: D
authors: Barford
authors: Robert
authors: R
authors: Downham
authors: Michelle D
authors: MD
authors: Garrett
authors: Robin A
authors: RA
authors: Carr
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D008024:Ligands; D008958:Models, Molecular; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C520852:5-methyl-4-phenyl-1H-pyrazole; D000970:Antineoplastic Agents; D008024:Ligands; D011720:Pyrazoles; D011993:Recombinant Fusion Proteins; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases