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 conferencePoster

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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 languageEnglish
PagesBook of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France
Number of pages1
Publication statusPublished - 2011
EventXVIIIeme JOURNEE JEUNES CHERCHEURS - Paris, Faculte de Pharmacie, France
Duration: 4 Feb 2011 → …

Conference

ConferenceXVIIIeme JOURNEE JEUNES CHERCHEURS
CityParis, Faculte de Pharmacie, France
Period4/02/11 → …

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Tryptophan
Tumors
Screening
Cells
Degradation
Enzymes

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Dolusic, E., Blanc, S., Larrieu, P., Moineaux, L., Colette, D., Fraser, G., ... 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, .
Dolusic, Eduard ; Blanc, Sébastien ; Larrieu, Pierre ; Moineaux, Laurence ; Colette, Delphine ; Fraser, Graeme ; Stroobant, Vincent ; Pilotte, Luc ; Colau, Didier ; Wouters, Johan ; Masereel, Bernard ; Van den Eynde, Benoît ; Frédérick, Raphaël. / Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy. Poster session presented at XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France, .1 p.
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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",
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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; Moineaux, Laurence; Colette, Delphine; Fraser, Graeme; Stroobant, Vincent; Pilotte, Luc; Colau, Didier; Wouters, Johan; Masereel, Bernard; Van den Eynde, Benoît; Frédérick, Raphaël.

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 conferencePoster

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

ER -

Dolusic E, Blanc S, Larrieu P, Moineaux L, Colette D, Fraser G et al. Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy. 2011. Poster session presented at XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France, .