Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase.
Pim-1 kinase is a cytoplasmic serine/threonine kinase that controls programmed cell death by phosphorylating substrates that regulate both apoptosis and cellular metabolism. A series of 2-styrylquinolines and quinoline-2-carboxamides has been identified as potent inhibitors of the Pim-1 kinase. The 8-hydroxy-quinoline 7-carboxylic acid moiety appeared to be a crucial pharmacophore for activity. Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency.
Sliman
Faten
F
UMR 89076 BIOCIS, Faculté de Pharmacie, Université Paris Sud, 5 rue J.-B. Clément, 92296 Châtenay-Malabry, France.
Blairvacq
Mélina
M
Durieu
Emilie
E
Meijer
Laurent
L
Rodrigo
Jordi
J
Desmaële
Didier
D
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D051573:Proto-Oncogene Proteins c-pim-1