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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages7595-7603
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number24
DOIs
Publication statusPublished - 15 Dec 2013

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Hydrazines
Indoleamine-Pyrrole 2,3,-Dioxygenase
hydrazine
Enzymes
Heme
Inhibitory Concentration 50
Immune system
Computer Simulation
Tumors
Immune System
Screening
Derivatives
2-hydrazinobenzothiazole
Neoplasms

Cite this

Fung, Sai Parng S ; Wang, Haiyan ; Tomek, Petr ; Squire, Christopher J. ; Flanagan, Jack U. ; Palmer, Brian D. ; Bridewell, David J A ; Tijono, Sofian M. ; Jamie, Joanne F. ; Ching, Lai Ming. / Discovery and characterisation of hydrazines as inhibitors of the immune suppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1). In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 24. pp. 7595-7603.
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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.",
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Fung, SPS, Wang, H, Tomek, P, Squire, CJ, Flanagan, JU, Palmer, BD, Bridewell, DJA, Tijono, SM, Jamie, JF & Ching, LM 2013, 'Discovery and characterisation of hydrazines as inhibitors of the immune suppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1)', Bioorganic and Medicinal Chemistry, vol. 21, no. 24, pp. 7595-7603. https://doi.org/10.1016/j.bmc.2013.10.037

Discovery and characterisation of hydrazines as inhibitors of the immune suppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1). / Fung, Sai Parng S; Wang, Haiyan; Tomek, Petr; Squire, Christopher J.; Flanagan, Jack U.; Palmer, Brian D.; Bridewell, David J A; Tijono, Sofian M.; Jamie, Joanne F.; Ching, Lai Ming.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 24, 15.12.2013, p. 7595-7603.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wang, Haiyan

AU - Tomek, Petr

AU - Squire, Christopher J.

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AU - Ching, Lai Ming

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