Abstract
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
| Original language | English |
|---|---|
| Pages | Book of Abstracts, Heterocycles in Bio-organic Chemistry, Riga, Latvia, 27 - 30 May 2013, PO129 |
| Number of pages | 1 |
| Publication status | Published - 27 May 2013 |
| Event | Heterocycles in Bio-organic Chemistry - Riga, Latvia Duration: 27 May 2013 → 30 May 2013 |
Conference
| Conference | Heterocycles in Bio-organic Chemistry |
|---|---|
| Country | Latvia |
| City | Riga |
| Period | 27/05/13 → 30/05/13 |
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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 session presented at Heterocycles in Bio-organic Chemistry, Riga, Latvia.Research output: Contribution to conference › 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 -