Authors: MariaWinters, 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
Publication Type: Journal Article
Source: European Journal of Medicinal Chemistry, Volume 162, 15 January 2019, Pages 455-464
Abstract: 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.