@article{TEXTUAL,
      recid = {14604},
      author = {Monsen, Paige J. and Bommi, Prashant V. and Grigorescu,  Arabela A. and Lauing, Kristen L. and Mao, Yingyu and  Berardi, Payton and Zhai, Lijie and Ojo, Oluwatomilayo and  Penco-Campillo, Manon and Koch, Taylor and Egozi, Michael  and Jha, Sonam and Dunne, Sara F. and Jiang, Hong and Song,  Guiqin and Zhang, Fang and Kregel, Steven and Vaziri-Gohar,  Ali and Fanning, Sean W. and Sanchez-Gomez, Pilar and  Yamini, Bakhtiar},
      title = {Rational Design and Optimization of a Potent IDO1  Proteolysis Targeting Chimera (PROTAC)},
      journal = {Journal of Medicinal Chemistry},
      address = {2025-02-13},
      number = {TEXTUAL},
      abstract = {Indoleamine 2,3-dioxygenase 1 (IDO1) is an  immunosuppressive protein that inhibits antitumor immunity  through both tryptophan metabolism and nonenzymatic  functions. Drugs targeting IDO1 enzyme activity have failed  to improve the overall survival of patients with cancer.  Developing new therapeutics that neutralize both enzyme-  and nonenzyme-derived immunosuppressive IDO1 effects is  therefore of high interest. We previously described a novel  proteolysis targeting chimera (PROTAC), NU223612, that  degrades IDO1 in cultured human glioblastoma (GBM) cells,  as well as in well-established brain tumors, in vivo. In  this study, we rationally optimized the structure of our  lead series to create NU227326, which degrades IDO1 with a  DC50 of 5 nM in human GBM cells. Mechanistic studies showed  that IDO1 degradation occurred through the  ubiquitin–proteasome system and was sustained for at least  2 days, supporting NU227326 as a highly potent IDO1 PROTAC  suitable for further studies in GBM and other human  cancers.},
      url = {http://knowledge.uchicago.edu/record/14604},
}