title: Selective bisubstrate inhibitors with sub-nanomolar affinity for protein kinase Pim-1.
abstract: Potent and selective: The unique nature of the ATP binding pocket structure of Pim family protein kinases (PKs) was used for the development of bisubstrate inhibitors and a fluorescent probe with sub-nanomolar affinity. Conjugates of arginine-rich peptides with two ATP mimetic scaffolds were synthesized and tested as inhibitors of Pim-1. Against a panel of 124 protein kinases, a novel ARC-PIM conjugate selectively inhibited PKs of the Pim family.
authors.affiliation: Institute of Chemistry, University of Tartu, Tartu, Estonia.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ekambaram
authors.forename: Erki
authors.initials: E
authors.lastname: Enkvist
authors.forename: Angela
authors.initials: A
authors.lastname: Vaasa
authors.forename: Marje
authors.initials: M
authors.lastname: Kasari
authors.forename: Gerda
authors.initials: G
authors.lastname: Raidaru
authors.forename: Stefan
authors.initials: S
authors.lastname: Knapp
authors.forename: Asko
authors.initials: A
authors.lastname: Uri
mesh_terms: D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1