Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing.
|Abstract||There is a growing recognition of the importance of protein kinases in the control of alternative splicing. To define the underlying regulatory mechanisms, highly selective inhibitors are needed. Here, we report the discovery and characterization of the dichloroindolyl enaminonitrile KH-CB19, a potent and highly specific inhibitor of the CDC2-like kinase isoforms 1 and 4 (CLK1/CLK4). Cocrystal structures of KH-CB19 with CLK1 and CLK3 revealed a n ... [truncated at 450 characters in length]|
|Author||Fedorov, Oleg; Huber, Kilian; Eisenreich, Andreas; et al|
|Subject||Alternative Splicing Catalytic Domain Endothelial Cells Heterocyclic Compounds, 2-Ring Humans Models, Molecular Nitriles Phosphorylation Protein Kinase Inhibitors Protein-Serine-Threonine Kinases Protein-Tyrosine Kinases RNA, Messenger RNA-Binding Proteins Substrate Specificity Thromboplastin drug effects drug effects metabolism chemical synthesis chemistry pharmacology chemical synthesis chemistry pharmacology drug effects chemical synthesis chemistry pharmacology antagonists and inhibitors chemistry metabolism antagonists and inhibitors chemistry metabolism genetics metabolism genetics|