title: Novel potent dual inhibitors of CK2 and Pim kinases with antiproliferative activity against cancer cells.
abstract: A novel family of potent dual inhibitors of CK2 and the Pim kinases was discovered by modifying the scaffolds of tricyclic Pim inhibitors. Several analogs were active at single digit nanomolar IC(50) values against CK2 and the Pim isoforms Pim-1 and Pim-2. The molecules displayed antiproliferative activity in various cell phenotypes in the low micromolar and submicromolar range, providing an excellent starting point for further drug discovery optimization.
authors.affiliation: Cylene Pharmaceuticals, 5820 Nancy Ridge Drive, Suite 200, San Diego, CA 92121, USA. fpierre@cylenepharma.com
authors.forename: Fabrice
authors.initials: F
authors.lastname: Pierre
authors.forename: Collin F
authors.initials: CF
authors.lastname: Regan
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Chevrel
authors.forename: Adam
authors.initials: A
authors.lastname: Siddiqui-Jain
authors.forename: Diwata
authors.initials: D
authors.lastname: Macalino
authors.forename: Nicole
authors.initials: N
authors.lastname: Streiner
authors.forename: Denis
authors.initials: D
authors.lastname: Drygin
authors.forename: Mustapha
authors.initials: M
authors.lastname: Haddach
authors.forename: Sean E
authors.initials: SE
authors.lastname: O'Brien
authors.forename: William G
authors.initials: WG
authors.lastname: Rice
authors.forename: David M
authors.initials: DM
authors.lastname: Ryckman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D055808:Drug Discovery; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim