Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).

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Tác giả: Jacob M Allen, Payton Berardi, Prashant V Bommi, Sara F Dunne, Michael Egozi, Sean Fanning, Arabela A Grigorescu, Sonam V Jha, Hong Jiang, Taylor Koch, Steven Kregel, Kristen L Lauing, Rimas V Lukas, Yingyu Mao, Paige J Monsen, Oluwatomilayo Ojo, Manon Penco-Campillo, Pilar Sanchez-Gomez, Gary E Schiltz, Guiqin Song, Ali Vaziri-Gohar, Derek A Wainwright, Bakhtiar Yamini, Lijie Zhai, Fang Zhang

Ngôn ngữ: eng

Ký hiệu phân loại: 519.57 Design of experiments

Thông tin xuất bản: United States : bioRxiv : the preprint server for biology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 179066

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest. We previously described the development of a novel Proteolysis Targeting Chimera (PROTAC), NU223612, that degrades IDO1 in cultured human glioblastoma (GBM) cells, as well as in well-established brain tumors,
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