Discovery of Potent 2-Aryl-6,7-Dihydro-5HPyrrolo[ 1,2-a]imidazoles as WDR5 WIN-site Inhibitors Using Fragment-Based Methods and Structure-Based Design

Displacement of WDR5 from Chromatin by a WIN Site Inhibitor with Picomolar Affinity.

SATQSKPTPVKPNYALKFTLAGHTKAVSSVKFSPNGEWLASSSADKLIKIWGAYDGKFEKTISGHKLGISDVAWSSDSNL
LVSASDDKTLKIWDVSSGKCLKTLKGHSNYVFCCNFNPQSNLIVSGSFDESVRIWDVKTGKCLKTLPAHSDPVSAVHFNR
DGSLIVSSSYDGLCRIWDTASGQCLKTLIDDDNPPVSFVKFSPNGKYILAATLDNTLKLWDYSKGKCLKTYTGHKNEKYC
IFANFSVTGGKWIVSGSEDNLVYIWNLQTKEIVQKLQGHTDVVISTACHPTENIIASAALENDKTIKLWKSDC

0.1 M Bis-Tris pH 6.0 or Hepes pH 7.5, 0.2 M ammonium acetate, 28% to 32% PEG3350

National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
WDR5-MLL1 NExT Leidos Biomedical Research 16X117 HHSN2162008000 01E UNIV 57992

WDR5, WIN-site, fragment screening, structure-based design, mixed-lineage leukemia, DNA BINDING PROTEIN, dna binding protein-inhibitor complex, GENE REGULATION, gene regulation-inhibitor complex