title: The Protein kinase inhibitor balanol: structure-activity relationships and structure-based computational studies.
abstract: Balanol, a fungal metabolite, is a potent ATP-competitive inhibitor of Protein Kinase C (PKC) and Protein Kinase A (PKA), important targets in oncology. Since its discovery in 1993, a number of studies have been performed in order to design selective and bioavailable balanol analogs. Several crystal structures of PKA in complex with balanol and a few analogs bound within the catalytic site have also been solved providing insight about the key interactions for binding. The PKA-balanol complex has also served as an interesting model system for structure-based ligand design and validation of a number of computational methodologies aimed at both understanding the physical basis for molecular recognition and addressing the important issue of protein flexibility in ligand binding. We provide an overview of the structure-activity relationships of balanol analogs and summarize the progress made in structural and computational studies involving balanol.
authors.affiliation: Departamento de Farmacología, Universidad de Alcalá, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Vineet
authors.initials: V
authors.lastname: Pande
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
mesh_terms: D000595:Amino Acid Sequence; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D019295:Computational Biology; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry* / Q000494:pharmacology*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D062385:Hydroxybenzoates; D047428:Protein Kinase Inhibitors; C015405:ophiocordin