title: Indolyl-naphthyl-maleimides as potent and selective inhibitors of protein kinase C-α/β.
abstract: The indolyl-naphthyl maleimide 7 is a potent inhibitor of the classical PKC isotypes α,β and shows excellent selectivity over the novel PKC isotypes δ,ε,η,θ and other kinases belonging to the AGC family. The SAR around 7 as well as the physico-chemical characteristics of selected derivatives and their activity in T and B cell activation and proliferation assays are discussed.
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland. Electronic address: maurice.van_eis@novartis.com.
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: van Eis
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: JeanPierre
authors.initials: J
authors.lastname: Evenou
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Schuler
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Zenke
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Vangrevelinghe
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Juergen
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Novartis Institutes for BioMedical Research, Forum 1, Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: von Matt
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D009284:Naphthols / Q000737:chemistry; D011485:Protein Binding; D064546:Protein Kinase C beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D009284:Naphthols; D047428:Protein Kinase Inhibitors; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha
keywords: B-cell activation; Inhibitors; PKC alpha/beta; T-cell activation