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

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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
Etat de la publicationPublié - 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

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    • 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 événementParticipation à une conférence, un congrès

    EFMC-ISMC 2010 XXIst INTERNATIONAL SYMPOSIUM ON MEDICINAL CHEMISTRY

    Eduard Dolusic (Poster)

    5 sept. 20109 sept. 2010

    Activité: Types de Participation ou d'organisation d'un événementParticipation 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

    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.