Basic Information
ID: ALA3085691
Journal: J Med Chem
Title: Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3-dioxygenase with therapeutic activity in Lewis lung cancer (LLC) tumor-bearing mice.
Authors: Yang S, Li X, Hu F, Li Y, Yang Y, Yan J, Kuang C, Yang Q.
Abstract: Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3(+) regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.
CiteXplore: 24099220
DOI: 10.1021/jm401195n
Patent ID: ┄
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