title: K252a is a potent and selective inhibitor of phosphorylase kinase.
abstract: The inhibition of phosphorylase kinase by a number of protein kinase inhibitors was examined. Both K252a and staurosporine are potent inhibitors of phosphorylase kinase with IC50 values of 1.7 nM and 0.5 nM respectively. K252a shows a 300-fold selectivity for this enzyme over protein kinase C whereas staurosporine shows only a 20-fold selectivity for phosphorylase kinase. In contrast, the Roche bis-indolyl maleimides inhibit phosphorylase kinase with IC50 values of approximately 1 microM and are highly selective for protein kinase C.
authors.affiliation: Roche Products Limited Welwyn Garden City, Herts, UK.
authors.forename: L H
authors.initials: LH
authors.lastname: Elliott
authors.forename: S E
authors.initials: SE
authors.lastname: Wilkinson
authors.forename: A D
authors.initials: AD
authors.lastname: Sedgwick
authors.forename: C H
authors.initials: CH
authors.lastname: Hill
authors.forename: G
authors.initials: G
authors.lastname: Lawton
authors.forename: P D
authors.initials: PD
authors.lastname: Davis
authors.forename: J S
authors.initials: JS
authors.lastname: Nixon
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D010764:Phosphorylase Kinase / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011817:Rabbits; D019311:Staurosporine; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049985:staurosporine aglycone; D010764:Phosphorylase Kinase; D019311:Staurosporine