Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain
datasetposted on 04.04.2017, 00:00 by R. Aldrin Denny, Andrew C. Flick, Jotham Coe, Jonathan Langille, Arindrajit Basak, Shenping Liu, Ingrid Stock, Parag Sahasrabudhe, Paul Bonin, Duncan A. Hay, Paul E. Brennan, Mathew Pletcher, Lyn H. Jones, Eugene L. Piatnitski Chekler
Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).
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BRD 4 proteinstructure-based drug designaddress bromodomain selectivity issuespermeability attributesoptimization processStructure-Based DesignCREB binding proteinSelective inhibitorsMedicinal chemistry optimizationtarget validationchemical probesSelective InhibitorsCREB Binding Protein Bromodomain Chemical probesCREBBP