Small-molecule inhibitors of PPI with primary epitopes. A) Crystal structure of BRD4 bromodomain (white surface) bound to (+)-JQ1 (green sticks, PDB: 3MXF) overlaid with acetylated histone peptide (magenta cartoon, PDB: 2WP1). Clinical compounds or their closest published analogs are shown below. B) Crystal structure of the dimerization interface of HIV integrase (white and cyan surface) bound to compound 16 (green sticks, PDB: 4NYF) with overlaid epitope from LEDGF (magenta, PDB: 2B4J). Compound 16 is a precursor to the clinical compound BI 224436. C) Von-Hippel Lindau (VHL) protein (white surface) with bound inhibitor compound 51 (green sticks, PDB: 4B9K). The central hydroxyproline mimics the binding of a peptide derived from HIF1α (PDB: 4AJY, not shown).