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Description: GSK1379725A (AU1) is the first small molecule selective for BPTF over Brd4, as an inhibitor of Brd4 and a selective BPTF ligand with Kd of 2.8 uM. AU1 is active in a cell-based reporter assay. No binding is detected with Brd4. Three new Brd4 inhibitors with submicromolar affinity were also discovered. Brd4 hits were validated in a thermal stability assay and potency determined via fluorescence anisotropy. The speed, ease of interpretation, and low protein concentration needed for protein-observed (19)F NMR experiments in a multiprotein format offers a new method to discover and characterize selective ligands for bromodomain-containing proteins.
References: ACS Chem Biol. 2015 Oct 16; 10(10):2246-56.
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