% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Deutscher:298619,
      author       = {R. C. E. Deutscher and C. Meyners and M. L. Repity and W.
                      O. Sugiarto and J. M. Kolos and E. V. S. Maciel and T.
                      Heymann and T. M. Geiger and S. Knapp$^*$ and F. Lermyte and
                      F. Hausch},
      title        = {{D}iscovery of fully synthetic {FKBP}12-m{TOR} molecular
                      glues.},
      journal      = {Chemical science},
      volume       = {16},
      number       = {10},
      issn         = {2041-6520},
      address      = {Cambridge},
      publisher    = {RSC},
      reportid     = {DKFZ-2025-00319},
      pages        = {4256-4263},
      year         = {2025},
      note         = {2025 Jan 13;16(10):4256-4263},
      abstract     = {Molecular glues are a new drug modality with the potential
                      to engage otherwise undruggable targets. However, the
                      rational discovery of molecular glues for desired targets is
                      a major challenge and most known molecular glues have been
                      discovered by serendipity. Here we present the first fully
                      synthetic FKBP12-mTOR molecular glues, which were discovered
                      from a FKBP-focused, target-unbiased ligand library. Our
                      biochemical screening of >1000 in-house FKBP ligands yielded
                      one hit that induced dimerization of FKBP12 and the FRB
                      domain of mTOR. The crystal structure of the ternary complex
                      revealed that the hit targeted a similar surface on the FRB
                      domain compared to natural product rapamycin but with a
                      radically different interaction pattern. Structure-guided
                      optimization improved potency 500-fold, and led to compounds
                      which initiate FKBP12-FRB complex formation in cells. Our
                      results show that molecular glues targeting flat surfaces
                      can be discovered by focused screening and support the use
                      of FKBP12 as a versatile presenter protein for molecular
                      glues.},
      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:39916884},
      pmc          = {pmc:PMC11796051},
      doi          = {10.1039/D4SC06917J},
      url          = {https://inrepo02.dkfz.de/record/298619},
}