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@ARTICLE{Hoffmann:304501,
      author       = {L. Hoffmann and C. Lenz and F. Farges and S. W. Kimani and
                      J. Dopfer and S. Keller and M. P. Schwalm$^*$ and H.
                      Holzmann and A. Kraemer and A. Dong and F. Li and I. Chau
                      and L. Halabelian and M. Gstaiger and S. Müller and S.
                      Knapp$^*$ and V. Němec},
      title        = {{D}iscovery of an exquisitely selective {WDR}5 chemical
                      probe accelerated by a high-quality {DEL}-{ML} {H}it.},
      journal      = {RSC chemical biology},
      volume       = {nn},
      issn         = {2633-0679},
      address      = {Cambridge},
      publisher    = {The Royal Society of Chemistry},
      reportid     = {DKFZ-2025-01890},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {Herein we present the rapid development of LH168, a potent
                      and highly selective chemical probe for WDR5, streamlined by
                      utilizing a DEL-ML (DNA encoded library-machine learning)
                      hit as the chemical starting point. LH168 was
                      comprehensively characterized in bioassays and demonstrated
                      potent in cellulo target engagement at the WIN-site pocket
                      of WDR5, with an EC50 of approximately 10 nM, a long
                      residence time, and exceptional proteome-wide selectivity
                      for WDR5. In addition, we present the X-ray co-crystal
                      structure and provide insights into the structure-activity
                      relationships (SAR). In parallel, we developed a matched
                      negative control compound as well as an alkyne analog
                      (compound 16) to facilitate the development of bifunctional
                      molecules. Taken together, we provide the scientific
                      community with a well-characterized chemical probe to enable
                      studies and functional manipulation of WDR5 in a cellular
                      context, as this protein represents a therapeutically
                      relevant target with scaffolding functions that influence
                      multiple cellular processes.},
      cin          = {FM01},
      ddc          = {540},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40927425},
      pmc          = {pmc:PMC12415533},
      doi          = {10.1039/D5CB00109A},
      url          = {https://inrepo02.dkfz.de/record/304501},
}