title: Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the indole orientation.
abstract: A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin dependant kinase. Inhibitory activities against the enzyme ranged from 10nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core of the inhibitors. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.
authors.affiliation: Scios, Inc., 6500 Paseo Padre Parkway, Fremont, CA 94555, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Perumattam
authors.forename: Dan-Xiong
authors.initials: DX
authors.lastname: Wang
authors.forename: Weiling
authors.initials: W
authors.lastname: Liang
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Xu
authors.forename: Steven
authors.initials: S
authors.lastname: Do
authors.forename: Llorente
authors.initials: L
authors.lastname: Bonaga
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Higaki
authors.forename: Hanmin
authors.initials: H
authors.lastname: Dong
authors.forename: Albert
authors.initials: A
authors.lastname: Liclican
authors.forename: Steve
authors.initials: S
authors.lastname: Sideris
authors.forename: Maureen
authors.initials: M
authors.lastname: Laney
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dugar
authors.forename: Babu
authors.initials: B
authors.lastname: Mavunkel
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Levy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008301:Maleimides / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D000255:Adenosine Triphosphate; C517660:CAMK2D protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2