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
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 |
| état | 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 |
Empreinte digitale
Contient cette citation
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.