Discovery and characterisation of hydrazines as inhibitors of the immune suppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1)

Sai Parng S Fung, Haiyan Wang, Petr Tomek, Christopher J. Squire, Jack U. Flanagan, Brian D. Palmer, David J A Bridewell, Sofian M. Tijono, Joanne F. Jamie, Lai Ming Ching*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Screening of a fragment library identified 2-hydrazinobenzothiazole as a potent inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme expressed by tumours that suppresses the immune system. Spectroscopic studies indicated that 2-hydrazinobenzothiazole interacted with the IDO1 haem and in silico docking predicted that the interaction was through hydrazine. Subsequent studies of hydrazine derivatives identified phenylhydrazine (IC50 = 0.25 ± 0.07 μM) to be 32-fold more potent than 2-hydrazinobenzothiazole (IC50 = 8.0 ± 2.3 μM) in inhibiting rhIDO1 and that it inhibited cellular IDO1 at concentrations that were noncytotoxic to cells. Here, phenylhydrazine is shown to inhibit IDO1 through binding to haem.

Original languageEnglish
Pages (from-to)7595-7603
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number24
DOIs
Publication statusPublished - 15 Dec 2013

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