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

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 originale	Anglais
Pages	Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129
Nombre de pages	1
Etat de la publication	Publié - 27 mai 2013
Evénement	Heterocycles in Bio-organic Chemistry - Riga, Lettonie Durée: 27 mai 2013 → 30 mai 2013

Une conférence

Une conférence	Heterocycles in Bio-organic Chemistry
Pays	Lettonie
La ville	Riga
période	27/05/13 → 30/05/13

Accès au document

Dolusic PO129 Riga 2013Accepted author manuscript, 721 KB
Abstract Dolusic Riga Bioheterocycles 2013 real

Empreinte digitale Examiner les sujets de recherche de « 3-ALKENYL INDOLES AS TRYPTOPHAN 2,3-DIOXYGENASE INHIBITORS FOR THE ENHANCEMENT OF CANCER IMMUNOTHERAPY ». Ensemble, ils forment une empreinte digitale unique.

Projets

2 Terminé

tryptophane 2,3-dioxygénase

WOUTERS, J.

1/10/11 → 30/09/13

Projet: Recherche

Conception, synthèse et étude de modulateurs d'enzymes impliquées dans le métabolisme du tryptophane, et en particulier dans la voie de la kynurénine.

FREDERICK, R.

1/10/07 → 30/09/10

Projet: Recherche

Équipement

Physico-chimie et caractérisation (PC2)

Johan Wouters (!!Manager) & Carmela Aprile (!!Manager)

Plateforme technologique Caracterisation physico-chimiques

Equipement/installations: Plateforme technolgique

Activités

2 Participation à une conférence, un congrès

Heterocycles in Bio-organic Chemistry

Eduard Dolusic (Poster)

27 mai 2013

Activité: Types de Participation ou d'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: Types de Participation ou d'organisation d'un événement › Participation à une conférence, un congrès

Presse/médias

Mladi Ogulinac u ekipi koja je na tragu lijeka protiv raka

Eduard Dolusic

24/02/12

1 élément de Couverture média

Presse/Médias: Autre

USPJEH MLADOGA OGULINCA

Eduard Dolusic

24/02/12

1 élément de Couverture média

Presse/Médias: Autre

Ogulinac Eduard Dolušić nadomak otkriću lijeka protiv raka

Eduard Dolusic

23/02/12

1 élément de Couverture média

Presse/Médias: Autre

Thèses de l'étudiant

Caractérisation enzymatique et structurale d'inhibiteurs indoliques de la tryptophane 2,3-dioxygénase.: Mémoire présenté pour l'obtention du grade académique de Master en Chimie "Chimie du Vivant et des Nanomatériaux" : Finalité Spécialisée.

Author: Molle, N., 2012

Superviseur: Wouters, J. (Promoteur), Dolusic, E. (Jury), Moineaux, L. (Jury), Fonder, G. (Jury) & Leherte, L. (Jury)

Thèse de l'étudiant: Master types › Master en sciences chimiques

Contient cette citation

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. 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 Dolu{\v s}i{\'c} 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 = may,

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

T2 - Heterocycles in Bio-organic Chemistry

Y2 - 27 May 2013 through 30 May 2013

ER -