Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy

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

Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy

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

Research output: Contribution to conference › Poster

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Abstract

Anti-cancer vaccination has so far shown a limited efficacy because cancer cells develop mechanisms of resisting or escaping immune rejection. The enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the oxidative degradation of tryptophan, has been identified as an important actor in this process. It has been demonstrated that many human tumors express IDO in a constitutive manner. [1] The recent elucidation of the three-dimensional structure of IDO [2] provides a basis for the structure-based drug discovery and design of IDO inhibitors. In the present work, [3] we applied virtual screening to discover new IDO inhibitors. The potency of the most promising candidate (1) was confirmed in vitro (IC50 = 65 µM) and could be improved 5-fold by pharmacomodulations. A number of analogs were also active in a cellular test. A modeling study was undertaken in order to explain the SAR.

Original language	English
Pages	Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France
Number of pages	1
Publication status	Published - 2011
Event	XVIIIeme JOURNEE JEUNES CHERCHEURS - Paris, Faculte de Pharmacie, France Duration: 4 Feb 2011 → …

Conference

Conference	XVIIIeme JOURNEE JEUNES CHERCHEURS
City	Paris, Faculte de Pharmacie, France
Period	4/02/11 → …

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71518Submitted manuscript, 228 KB

3 Article
2 Poster
2 Literature review

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 and 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., Wouters, J., Dolušić, E., FREDERICK, R., POUYEZ, J., Van den Eynde, B. J., Frère, J., Moser, M., Jean-Marie, B., Combalbert, J. & Stephenne, J.
1/04/08 → 31/03/12
Project: Research

Physical Chemistry and characterization(PC2)
Johan Wouters (Manager) & Carmela Aprile (Manager)
Technological Platform Physical Chemistry and characterization
Facility/equipment: Technological Platform

4 Participation in conference

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

Cite this

Dolusic, E., Blanc, S., Larrieu, P., Moineaux, L., Colette, D., Fraser, G., Stroobant, V., Pilotte, L., Colau, D., Wouters, J., Masereel, B., Van den Eynde, B., & Frédérick, R. (2011). Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy. Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France. Poster session presented at XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France.

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title = "Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy",

abstract = "Anti-cancer vaccination has so far shown a limited efficacy because cancer cells develop mechanisms of resisting or escaping immune rejection. The enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the oxidative degradation of tryptophan, has been identified as an important actor in this process. It has been demonstrated that many human tumors express IDO in a constitutive manner. [1] The recent elucidation of the three-dimensional structure of IDO [2] provides a basis for the structure-based drug discovery and design of IDO inhibitors. In the present work, [3] we applied virtual screening to discover new IDO inhibitors. The potency of the most promising candidate (1) was confirmed in vitro (IC50 = 65 µM) and could be improved 5-fold by pharmacomodulations. A number of analogs were also active in a cellular test. A modeling study was undertaken in order to explain the SAR.",

author = "Eduard Dolusic 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 Rapha{\"e}l Fr{\'e}d{\'e}rick",

year = "2011",

language = "English",

pages = "Book of Abstracts, XVIII{\`e}me Journ{\'e}e Jeunes Chercheurs, 04/02/11, Paris, France",

note = "XVIIIeme JOURNEE JEUNES CHERCHEURS ; Conference date: 04-02-2011",

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Dolusic, E, Blanc, S, Larrieu, P, Moineaux, L, Colette, D, Fraser, G, Stroobant, V, Pilotte, L, Colau, D, Wouters, J , Masereel, B, Van den Eynde, B & Frédérick, R 2011, 'Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy', XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France, 4/02/11 pp. Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France.

Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy. / Dolusic, Eduard; Blanc, Sébastien; Larrieu, Pierre et al.
2011. Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France Poster session presented at XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France.

Research output: Contribution to conference › Poster

TY - CONF

T1 - Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy

AU - Dolusic, Eduard

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 - Frédérick, Raphaël

PY - 2011

Y1 - 2011

N2 - Anti-cancer vaccination has so far shown a limited efficacy because cancer cells develop mechanisms of resisting or escaping immune rejection. The enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the oxidative degradation of tryptophan, has been identified as an important actor in this process. It has been demonstrated that many human tumors express IDO in a constitutive manner. [1] The recent elucidation of the three-dimensional structure of IDO [2] provides a basis for the structure-based drug discovery and design of IDO inhibitors. In the present work, [3] we applied virtual screening to discover new IDO inhibitors. The potency of the most promising candidate (1) was confirmed in vitro (IC50 = 65 µM) and could be improved 5-fold by pharmacomodulations. A number of analogs were also active in a cellular test. A modeling study was undertaken in order to explain the SAR.

AB - Anti-cancer vaccination has so far shown a limited efficacy because cancer cells develop mechanisms of resisting or escaping immune rejection. The enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the oxidative degradation of tryptophan, has been identified as an important actor in this process. It has been demonstrated that many human tumors express IDO in a constitutive manner. [1] The recent elucidation of the three-dimensional structure of IDO [2] provides a basis for the structure-based drug discovery and design of IDO inhibitors. In the present work, [3] we applied virtual screening to discover new IDO inhibitors. The potency of the most promising candidate (1) was confirmed in vitro (IC50 = 65 µM) and could be improved 5-fold by pharmacomodulations. A number of analogs were also active in a cellular test. A modeling study was undertaken in order to explain the SAR.

M3 - Poster

SP - Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France

T2 - XVIIIeme JOURNEE JEUNES CHERCHEURS

Y2 - 4 February 2011

ER -

Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy

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