title: Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases.
abstract: A series of novel 3,5-disubstituted indole derivatives as potent and selective inhibitors of all three members of the Pim kinase family is described. High throughput screen identified a pan-Pim kinase inhibitor with a promiscuous scaffold. Guided by structure-based drug design, SAR of the series afforded a highly selective indole chemotype that was further developed into a potent set of compounds against Pim-1, 2, and 3 (Pim-1 and Pim-3: IC(50)≤2nM and Pim-2: IC(50)≤100nM).
authors.affiliation: Global Discovery Chemistry/Oncology and Exploratory Chemistry, Novartis Institutes of BioMedical Research, Emeryville, CA 94608, USA. gisele.nishiguchi@novartis.com
authors.forename: Gisele A
authors.initials: GA
authors.lastname: Nishiguchi
authors.forename: Gordana
authors.initials: G
authors.lastname: Atallah
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bellamacina
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Burger
authors.forename: Yu
authors.initials: Y
authors.lastname: Ding
authors.forename: Paul H
authors.initials: PH
authors.lastname: Feucht
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Garcia
authors.forename: Wooseok
authors.initials: W
authors.lastname: Han
authors.forename: Liana
authors.initials: L
authors.lastname: Klivansky
authors.forename: Mika
authors.initials: M
authors.lastname: Lindvall
mesh_terms: D055808:Drug Discovery; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases