% 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{Kotlarek:632973,
      author       = {Kotlarek, Daria and Dudek, Katarzyna and Woźniak, Bartosz
                      and Pastok, Martyna and Shishov, Dmitrii and Cottens,
                      Sylvain and Biśta, Michał and Krzywiecka, Emilia and
                      Górecka-Minakowska, Karolina and Jurczak, Kinga and Drmota,
                      Tomas and Adamczyk, Justyna and Faliński, Szymon and
                      Gajewska, Daria and Klejnot, Marta and Król, Aleksandra and
                      Cuprych-Belter, Monika and Mames, Iwona and Mathieu, Arnaud
                      and Podkówka, Aleksandra and Przytulski, Kamil and Skowron,
                      Alicja N. and Sypień, Magdalena and Takagi, Toshimitsu and
                      Wanat, Weronika and Wierzbicki, Igor H. and Wisniewski,
                      Janusz and Szlachcic, Anna and Pokładek, Ziemowit and
                      Walczak, Michał J.},
      title        = {{E}xploration of chemical probes and conformational
                      flexibility of {GID}4 - the substrate receptor of human
                      {CTLH} {E}3 ligase complex},
      address      = {Biorxiv},
      reportid     = {PUBDB-2025-02299},
      year         = {2025},
      note         = {Door proposal: P-20010353; INDU-22-L03 - Captor
                      Therapeutics Inc., long-term agreementThe project nr
                      POIR.01.01.01-00-0931/19 “Development of an integrated
                      technology platform in the field of targeted protein
                      degradation and its implementation to the pharmaceutical
                      market” was co-financed by the European Regional
                      Development Fund.},
      abstract     = {The application of targeted protein degradation (TPD) is
                      currently constrained by the limited availability of
                      low-molecular-weight molecules that can recruit E3 ligases
                      other than CRBN (Cereblon) or VHL (Von Hippel-Lindau
                      ligase). In this study, we present the structure-based drug
                      design (SBDD) of high-affinity ligands that engage E3 ligase
                      GID4 (Glucose-induced degradation protein 4) in biophysical
                      and cellular experiments. Through structural studies and
                      molecular modeling, we identified three groups (clusters) of
                      compounds that induce distinct conformations of GID4. We
                      identified potential exit vectors and used the most
                      promising ligand as a building block to prepare bifunctional
                      degraders in the form of proteolysis-targeting chimeras
                      (PROTACs). Although ternary complex formation was successful
                      in vitro, degradation of BRD4 was not observed, highlighting
                      the need for further optimization of the degraders. We also
                      theoretically investigated the likelihood of the identified
                      GID4 conformations participating in protein-protein
                      interactions mediated by molecular glue mechanisms. We
                      believe the expanded ligand diversity discovered in this
                      study may pave the way for tuning the selectivity and
                      efficacy of protein-protein interactions involving GID4 and
                      its neosubstrates.},
      cin          = {DOOR ; HAS-User},
      cid          = {I:(DE-H253)HAS-User-20120731},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P11-20150101},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/2025.07.01.662521},
      url          = {https://bib-pubdb1.desy.de/record/632973},
}