Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase

Maria Winters, 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

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)455-464
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume162
DOIs
StatePublished - Jan 15 2019

Keywords

  • Antitumor therapy
  • Diaryl oalkylhydroxylamines
  • Dual inhibitor
  • IDO1 inhibition
  • IDO2 inhibition
  • Pan inhibition
  • TDO inhibition

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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    Winters, M., DuHadaway, J. B., Pham, K. N., Lewis-Ballester, A., Badir, S., Wai, J., Sheikh, E., Yeh, S. R., Prendergast, G. C., Muller, A. J., & Malachowski, W. P. (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. https://doi.org/10.1016/j.ejmech.2018.11.010