Organic Letters · 2018 · 66 citations · 12 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructural BiologyEnzyme InhibitionLead Compound DesignLigand BindingMolecular DockingProtein-ligand DockingStructure-activity Relationship AnalysisAnticancer ActivityBinding Mode AnalysisBinding Mode OptimizationBiological Evaluation ReportMonodentate Ligand BindingStructure-based Lead DiscoveryStructure-based Ligand DesignX-ray Structure Determination
The multicomponent synthesis of a mini-library of histone deacetylase inhibitors with imidazo[1,2- a]pyridine-based cap groups is presented. The biological evaluation led to the discovery of the hit compound MAIP-032 as a selective HDAC6 inhibitor with promising anticancer activity. The X-ray structure of catalytic domain 2 from Danio rerio HDAC6 complexed with MAIP-032 revealed a monodentate zinc-binding mode.
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Structural insights into HDAC6 tubulin deacetylation and its selective inhibition
Y. Miyake, J.J. Keusch, Longlong Wang et al. · Nature Chemical Biology · 2016 · 297 citations · Full text