Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy

Raphaël Frédérick, Sébastien Blanc, Pierre Larrieu, Laurence Moineaux, Delphine Colette, Graeme Fraser, Vincent Stroobant, Luc Pilotte, Didier Colau, Johan Wouters, Bernard Masereel, Benoît Van den Eynde, Eduard Dolusic

Research output: Contribution to conferencePoster

Abstract

Cancers and tumors regularly evade the immune surveillance system of the host employing several mechanisms. It was found previously that one mechanism resulting in tumoral immune resistance stems from the constitutive expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells1
The present work is based on the recent discovery that a second enzyme in tryptophan catabolism, tryptophan 2,3-dioxygenase (TDO), is also unexpectedly expressed in many tumor cells.2,3
This work4 describes the design, synthesis, X-ray structure determination, enzyme inhibition, cellular assays, docking and solubility tests of indole-based TDO inhibitors of the general structure 1. This strategy is based on similar compounds reported as dual TDO/5-HT reuptake inhibitors.5
Original languageEnglish
PagesPC.281, 21st ISMC, Brussels, Belgium, September 5-9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181-182
Number of pages2
Publication statusPublished - 2010
EventEFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY - Bruxelles, Belgium
Duration: 5 Sep 2010 → …

Conference

ConferenceEFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY
CountryBelgium
CityBruxelles
Period5/09/10 → …

Fingerprint

Tryptophan Oxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Tumors
Enzyme inhibition
Tryptophan
Assays
Serotonin
Solubility
X rays
Enzymes
indole

Cite this

Frédérick, R., Blanc, S., Larrieu, P., Moineaux, L., Colette, D., Fraser, G., ... Dolusic, E. (2010). Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy. PC.281, 21st ISMC, Brussels, Belgium, September 5-9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181-182. Poster session presented at EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY, Bruxelles, Belgium.
Frédérick, Raphaël ; Blanc, Sébastien ; Larrieu, Pierre ; Moineaux, Laurence ; Colette, Delphine ; Fraser, Graeme ; Stroobant, Vincent ; Pilotte, Luc ; Colau, Didier ; Wouters, Johan ; Masereel, Bernard ; Van den Eynde, Benoît ; Dolusic, Eduard. / Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy. Poster session presented at EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY, Bruxelles, Belgium.2 p.
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title = "Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy",
abstract = "Cancers and tumors regularly evade the immune surveillance system of the host employing several mechanisms. It was found previously that one mechanism resulting in tumoral immune resistance stems from the constitutive expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells1The present work is based on the recent discovery that a second enzyme in tryptophan catabolism, tryptophan 2,3-dioxygenase (TDO), is also unexpectedly expressed in many tumor cells.2,3This work4 describes the design, synthesis, X-ray structure determination, enzyme inhibition, cellular assays, docking and solubility tests of indole-based TDO inhibitors of the general structure 1. This strategy is based on similar compounds reported as dual TDO/5-HT reuptake inhibitors.5",
author = "Rapha{\"e}l Fr{\'e}d{\'e}rick and S{\'e}bastien Blanc and Pierre Larrieu and Laurence Moineaux and Delphine Colette and Graeme Fraser and Vincent Stroobant and Luc Pilotte and Didier Colau and Johan Wouters and Bernard Masereel and {Van den Eynde}, Beno{\^i}t and Eduard Dolusic",
year = "2010",
language = "English",
pages = "PC.281, 21st ISMC, Brussels, Belgium, September 5--9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181--182",
note = "EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY ; Conference date: 05-09-2010",

}

Frédérick, R, Blanc, S, Larrieu, P, Moineaux, L, Colette, D, Fraser, G, Stroobant, V, Pilotte, L, Colau, D, Wouters, J, Masereel, B, Van den Eynde, B & Dolusic, E 2010, 'Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy', EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY, Bruxelles, Belgium, 5/09/10 pp. PC.281, 21st ISMC, Brussels, Belgium, September 5-9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181-182.

Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy. / Frédérick, Raphaël; Blanc, Sébastien; Larrieu, Pierre; Moineaux, Laurence; Colette, Delphine; Fraser, Graeme; Stroobant, Vincent; Pilotte, Luc; Colau, Didier; Wouters, Johan; Masereel, Bernard; Van den Eynde, Benoît; Dolusic, Eduard.

2010. PC.281, 21st ISMC, Brussels, Belgium, September 5-9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181-182 Poster session presented at EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY, Bruxelles, Belgium.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy

AU - Frédérick, Raphaël

AU - Blanc, Sébastien

AU - Larrieu, Pierre

AU - Moineaux, Laurence

AU - Colette, Delphine

AU - Fraser, Graeme

AU - Stroobant, Vincent

AU - Pilotte, Luc

AU - Colau, Didier

AU - Wouters, Johan

AU - Masereel, Bernard

AU - Van den Eynde, Benoît

AU - Dolusic, Eduard

PY - 2010

Y1 - 2010

N2 - Cancers and tumors regularly evade the immune surveillance system of the host employing several mechanisms. It was found previously that one mechanism resulting in tumoral immune resistance stems from the constitutive expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells1The present work is based on the recent discovery that a second enzyme in tryptophan catabolism, tryptophan 2,3-dioxygenase (TDO), is also unexpectedly expressed in many tumor cells.2,3This work4 describes the design, synthesis, X-ray structure determination, enzyme inhibition, cellular assays, docking and solubility tests of indole-based TDO inhibitors of the general structure 1. This strategy is based on similar compounds reported as dual TDO/5-HT reuptake inhibitors.5

AB - Cancers and tumors regularly evade the immune surveillance system of the host employing several mechanisms. It was found previously that one mechanism resulting in tumoral immune resistance stems from the constitutive expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells1The present work is based on the recent discovery that a second enzyme in tryptophan catabolism, tryptophan 2,3-dioxygenase (TDO), is also unexpectedly expressed in many tumor cells.2,3This work4 describes the design, synthesis, X-ray structure determination, enzyme inhibition, cellular assays, docking and solubility tests of indole-based TDO inhibitors of the general structure 1. This strategy is based on similar compounds reported as dual TDO/5-HT reuptake inhibitors.5

M3 - Poster

SP - PC.281, 21st ISMC, Brussels, Belgium, September 5-9, 2010, Drugs of the Future, volume 35, issue suppl. A, pp. 181-182

ER -

Frédérick R, Blanc S, Larrieu P, Moineaux L, Colette D, Fraser G et al. Discovery and Optimization Of Indole-pyridinyl-ethanones as Novel Inhibitors of Indoleamine-2,3-Dioxygenase (IDO), a Promising Target for Anti-Cancer Immunotherapy. 2010. Poster session presented at EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY, Bruxelles, Belgium.