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

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

Namur Research Institute for Life Sciences

Research output: Contribution to conference › Poster

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 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
Number of pages	2
Publication status	Published - 2010
Event	EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY - Bruxelles, Belgium Duration: 5 Sept 2010 → …

Conference

Conference	EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY
Country/Territory	Belgium
City	Bruxelles
Period	5/09/10 → …

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

4 Poster
3 Article
3 Literature review
1 Conference contribution

Indoleamine 2,3-dioxygenase inhibitors: a patent review (2008-2012)
Dolušić, E. & Frédérick, R., 1 Oct 2013, In: Expert opinion on therapeutic targets. 23, 10, p. 1367-1381 15 p.
Research output: Contribution to journal › Literature review › peer-review
Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A
Dolušić, E., Larrieu, P., Meinguet, C., Colette, D., Rives, A., Blanc, S., Ferain, T., Pilotte, L., Stroobant, V., Wouters, J., Van Den Eynde, B., Masereel, B., Delfourne, E. & Frédérick, R., 1 Jan 2013, In: Bioorganic & Medicinal Chemistry Letters. 23, 1, p. 47-54 8 p.
Research output: Contribution to journal › Article › peer-review
3 Downloads (Pure)
Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors
Dolušić, E., Larrieu, P., Blanc, S., Sapunaric, F., Pouyez, J., Moineaux, L., Colette, D., Stroobant, V., Pilotte, L., Colau, D., Ferain, T., Fraser, G., Galleni, M., Frère, J.-M., Masereel, B., Van Den Eynde, B., Wouters, J. & Frédérick, R., 2011, In: European Journal of Medicinal Chemistry. 46, 7, p. 3058-3065 8 p.
Research output: Contribution to journal › Article › peer-review

1 Finished

CANTOL: Design and synthesis of indolamine dioxygenase (IDO) for the treatment of cancer
Masereel, B. (PI), Wouters, J. (PI), DOLUSIC, E. (Researcher), FREDERICK, R. (Researcher), POUYEZ, J. (Researcher), Van den Eynde, B. J. (CoI), Frère, J.-M. (CoI), Moser, M. (CoI), Jean-Marie, B. (CoI), Combalbert, J. (PI) & Stephenne, J. (CoI)
1/04/08 → 31/03/12
Project: Research

Physical Chemistry and characterization(PC2)
Wouters, J. (Manager), Aprile, C. (Manager) & Fusaro, L. (Manager)
Technological Platform Physical Chemistry and characterization
Facility/equipment: Technological Platform

3 Participation in conference

47th RICT: Drug Discovery and Selection.
Dolusic, E. (Poster)
6 Jul 2011 → 8 Jul 2011
Activity: Participating in or organising an event types › Participation in conference
XVIIIeme JOURNEE JEUNES CHERCHEURS
Dolusic, E. (Poster)
4 Feb 2011
Activity: Participating in or organising an event types › Participation in conference
EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY
Dolusic, E. (Poster)
5 Sept 2010 → 9 Sept 2010
Activity: Participating in or organising an event types › Participation in conference

Cite this

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. 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.

@conference{08dbfdaba4fb4dada4204ba695b2859f,

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 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",

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 et al.
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 conference › Poster

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 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

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 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

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

T2 - EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY

Y2 - 5 September 2010

ER -

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

Abstract

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