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

2 Citations (Scopus)

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

Fingerprint

Hydroxylamines
Indoleamine-Pyrrole 2,3,-Dioxygenase
Dioxygenases
Tryptophan
Enzymes
Immunosuppressive Agents
Neoplasms
Inflammation
Research

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase. / Winters, Maria; DuHadaway, James B.; Pham, Khoa N.; Lewis-Ballester, Ariel; Badir, Shorouk; Wai, Jenny; Sheikh, Eesha; Yeh, Syun-Ru; Prendergast, George C.; Muller, Alexander J.; Malachowski, William P.

In: European Journal of Medicinal Chemistry, Vol. 162, 15.01.2019, p. 455-464.

Research output: Contribution to journalArticle

Winters, M, DuHadaway, JB, Pham, KN, Lewis-Ballester, A, Badir, S, Wai, J, Sheikh, E, Yeh, S-R, Prendergast, GC, Muller, AJ & Malachowski, WP 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, vol. 162, pp. 455-464. https://doi.org/10.1016/j.ejmech.2018.11.010
Winters, Maria ; DuHadaway, James B. ; Pham, Khoa N. ; Lewis-Ballester, Ariel ; Badir, Shorouk ; Wai, Jenny ; Sheikh, Eesha ; Yeh, Syun-Ru ; Prendergast, George C. ; Muller, Alexander J. ; Malachowski, William P. / Diaryl hydroxylamines as pan or dual inhibitors of indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2 and tryptophan dioxygenase. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 162. pp. 455-464.
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