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

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Résumé

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.

langue originale	Anglais
Pages	Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France
Nombre de pages	1
Etat de la publication	Publié - 2011
Evénement	XVIIIeme JOURNEE JEUNES CHERCHEURS - Paris, Faculte de Pharmacie, France Durée: 4 févr. 2011 → …

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Une conférence	XVIIIeme JOURNEE JEUNES CHERCHEURS
La ville	Paris, Faculte de Pharmacie, France
période	4/02/11 → …

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Indoleamine 2,3-dioxygenase inhibitors: a patent review (2008-2012)
Dolušić, E. & Frédérick, R., 1 oct. 2013, Dans: Expert opinion on therapeutic targets. 23, 10, p. 1367-1381 15 p.
Résultats de recherche: Contribution à un journal/une revue › Revue de documentation › Revue par des pairs
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 janv. 2013, Dans: Bioorganic and medicinal chemistry letters. 23, 1, p. 47-54 8 p.
Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs
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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, Dans: European Journal of Medicinal Chemistry. 46, 7, p. 3058-3065 8 p.
Résultats de recherche: Contribution à un journal/une revue › Article › Revue par des pairs

1 Terminé

CANTOL: Conception et synthèse d'inhibiteurs de l'indolaminedioxygénase (IDO) pour le traitement du 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
Projet: Recherche

Physico-chimie et caractérisation (PC2)
Johan Wouters (!!Manager) & Carmela Aprile (!!Manager)
Plateforme technologique Caracterisation physico-chimiques
Equipement/installations: Plateforme technolgique

4 Participation à une conférence, un congrès

47th RICT: Drug Discovery and Selection.
Eduard Dolusic (Poster)
6 juil. 2011 → 8 juil. 2011
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès
XVIIIeme JOURNEE JEUNES CHERCHEURS
Eduard Dolusic (Poster)
4 févr. 2011
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès
EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY
Eduard Dolusic (Poster)
5 sept. 2010 → 9 sept. 2010
Activité: Participation ou organisation d'un événement › Participation à une conférence, un congrès

Contient cette citation

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 présenté � 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 p. 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 présenté � XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France.

Résultats de recherche: Contribution à un événement scientifique (non publié) › 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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