3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY

Eduard Dolušić, Luc Pilotte, Laurence Moineaux, Pierre Larrieu, Vincent Stroobant, Didier Colau, Lionel Pochet, Etienne De Plaen, Catherine Uyttenhove, Benoît Van den Eynde, Johan Wouters, Bernard Masereel, Steve Lanners, Raphaël Frédérick

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

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Résumé

Recently, our group has shown that tryptophan 2,3 dioxygenase (TDO), a hepatic enzyme catalyzing the first step of tryptophan degradation, is expressed in many tumors, thereby contributing to tumoral immune resistance.1 The complementary role of tryptophan catabolites has been demonstrated by others.2
We set out to develop new, improved TDO inhibitors using as the starting point the only (unoptimized) series previously known in the literature.3
Herein, we describe the syntheses and structure-activity studies around a series of 3-alkenyl indoles and their derivatives.4 The TDO inhibitory potency was evaluated and rationalized by molecular modeling studies, while solubility, stability and oral bioavailability were determined for selected compounds. The most promising candidate was evaluated in a preclinical model in mice where, upon systemic treatment, it indeed reversed TDO-mediated tumoral immune resistance.5
langue originaleAnglais
PagesBook of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129
Nombre de pages1
étatPublié - 27 mai 2013
EvénementHeterocycles in Bio-organic Chemistry - Riga, Lettonie
Durée: 27 mai 201330 mai 2013

Une conférence

Une conférenceHeterocycles in Bio-organic Chemistry
PaysLettonie
La villeRiga
période27/05/1330/05/13

Empreinte digitale

Tryptophan Oxygenase
Indoles
Tryptophan
Molecular modeling
Tumors
Solubility
Degradation
Enzymes

Citer ceci

Dolušić, E., Pilotte, L., Moineaux, L., Larrieu, P., Stroobant, V., Colau, D., ... Frédérick, R. (2013). 3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY. Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129. Poster présenté � Heterocycles in Bio-organic Chemistry, Riga, Lettonie.
Dolušić, Eduard ; Pilotte, Luc ; Moineaux, Laurence ; Larrieu, Pierre ; Stroobant, Vincent ; Colau, Didier ; Pochet, Lionel ; De Plaen, Etienne ; Uyttenhove, Catherine ; Van den Eynde, Benoît ; Wouters, Johan ; Masereel, Bernard ; Lanners, Steve ; Frédérick, Raphaël. / 3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY. Poster présenté � Heterocycles in Bio-organic Chemistry, Riga, Lettonie.1 p.
@conference{4d1fc42c865248918c4524a6d1fd3b9d,
title = "3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY",
abstract = "Recently, our group has shown that tryptophan 2,3 dioxygenase (TDO), a hepatic enzyme catalyzing the first step of tryptophan degradation, is expressed in many tumors, thereby contributing to tumoral immune resistance.1 The complementary role of tryptophan catabolites has been demonstrated by others.2We set out to develop new, improved TDO inhibitors using as the starting point the only (unoptimized) series previously known in the literature.3 Herein, we describe the syntheses and structure-activity studies around a series of 3-alkenyl indoles and their derivatives.4 The TDO inhibitory potency was evaluated and rationalized by molecular modeling studies, while solubility, stability and oral bioavailability were determined for selected compounds. The most promising candidate was evaluated in a preclinical model in mice where, upon systemic treatment, it indeed reversed TDO-mediated tumoral immune resistance.5",
author = "Eduard Dolušić and Luc Pilotte and Laurence Moineaux and Pierre Larrieu and Vincent Stroobant and Didier Colau and Lionel Pochet and {De Plaen}, Etienne and Catherine Uyttenhove and {Van den Eynde}, Beno{\^i}t and Johan Wouters and Bernard Masereel and Steve Lanners and Rapha{\"e}l Fr{\'e}d{\'e}rick",
year = "2013",
month = "5",
day = "27",
language = "English",
pages = "Book of Abstracts, Heterocycles in Bio--organic Chemistry, Riga, Latvia, 27 -- 30 May 2013, PO129",
note = "Heterocycles in Bio-organic Chemistry ; Conference date: 27-05-2013 Through 30-05-2013",

}

Dolušić, E, Pilotte, L, Moineaux, L, Larrieu, P, Stroobant, V, Colau, D, Pochet, L, De Plaen, E, Uyttenhove, C, Van den Eynde, B, Wouters, J, Masereel, B, Lanners, S & Frédérick, R 2013, '3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY' Heterocycles in Bio-organic Chemistry, Riga, Lettonie, 27/05/13 - 30/05/13, p. Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129.

3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY. / Dolušić, Eduard; Pilotte, Luc; Moineaux, Laurence; Larrieu, Pierre; Stroobant, Vincent; Colau, Didier; Pochet, Lionel; De Plaen, Etienne; Uyttenhove, Catherine; Van den Eynde, Benoît; Wouters, Johan; Masereel, Bernard; Lanners, Steve; Frédérick, Raphaël.

2013. Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129 Poster présenté � Heterocycles in Bio-organic Chemistry, Riga, Lettonie.

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

TY - CONF

T1 - 3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY

AU - Dolušić, Eduard

AU - Pilotte, Luc

AU - Moineaux, Laurence

AU - Larrieu, Pierre

AU - Stroobant, Vincent

AU - Colau, Didier

AU - Pochet, Lionel

AU - De Plaen, Etienne

AU - Uyttenhove, Catherine

AU - Van den Eynde, Benoît

AU - Wouters, Johan

AU - Masereel, Bernard

AU - Lanners, Steve

AU - Frédérick, Raphaël

PY - 2013/5/27

Y1 - 2013/5/27

N2 - Recently, our group has shown that tryptophan 2,3 dioxygenase (TDO), a hepatic enzyme catalyzing the first step of tryptophan degradation, is expressed in many tumors, thereby contributing to tumoral immune resistance.1 The complementary role of tryptophan catabolites has been demonstrated by others.2We set out to develop new, improved TDO inhibitors using as the starting point the only (unoptimized) series previously known in the literature.3 Herein, we describe the syntheses and structure-activity studies around a series of 3-alkenyl indoles and their derivatives.4 The TDO inhibitory potency was evaluated and rationalized by molecular modeling studies, while solubility, stability and oral bioavailability were determined for selected compounds. The most promising candidate was evaluated in a preclinical model in mice where, upon systemic treatment, it indeed reversed TDO-mediated tumoral immune resistance.5

AB - Recently, our group has shown that tryptophan 2,3 dioxygenase (TDO), a hepatic enzyme catalyzing the first step of tryptophan degradation, is expressed in many tumors, thereby contributing to tumoral immune resistance.1 The complementary role of tryptophan catabolites has been demonstrated by others.2We set out to develop new, improved TDO inhibitors using as the starting point the only (unoptimized) series previously known in the literature.3 Herein, we describe the syntheses and structure-activity studies around a series of 3-alkenyl indoles and their derivatives.4 The TDO inhibitory potency was evaluated and rationalized by molecular modeling studies, while solubility, stability and oral bioavailability were determined for selected compounds. The most promising candidate was evaluated in a preclinical model in mice where, upon systemic treatment, it indeed reversed TDO-mediated tumoral immune resistance.5

M3 - Poster

SP - Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129

ER -

Dolušić E, Pilotte L, Moineaux L, Larrieu P, Stroobant V, Colau D et al.. 3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY. 2013. Poster présenté � Heterocycles in Bio-organic Chemistry, Riga, Lettonie.