Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase
Author's Final Manuscript
European Journal of Medicinal Chemistry
Tryptophan (Trp) catabolizing enzymes play an important and complex role in the development of cancer. Significant evidence implicates them in a range of inflammatory and immunosuppressive activities. Whereas inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) have been reported and analyzed in the clinic, fewer inhibitors have been described for tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase-2 (IDO2) which also have been implicated more recently in cancer, inflammation and immune control. Consequently the development of dual or pan inhibitors of these Trp catabolizing enzymes may represent a therapeutically important area of research. This is the first report to describe the development of dual and pan inhibitors of IDO1, TDO and IDO2.
Winters, Maria, James B. DuHadaway, Khoa N. Pham, Ariel Lewis-Ballester, Shorouk Badir, Jenny Wai, Eesha Sheikh, Syun-Ru Yeh, George C. Prendergast, Alexander J. Muller, William P. Malachowski. 2019. "Diaryl Hydroxylamines as Pan or Dual Inhibitors of Indoleamine 2,3-Dioxygenase-1, Indoleamine 2,3-Dioxygenase-2 and Tryptophan Dioxygenase." European Journal of Medicinal Chemistry 162: 455-464.