Résumé
(IDO1) is an important mechanism of peripheral immune tolerance
contributing to tumoral immune resistance,[1] and IDO1 inhibition is
an active area of drug development.[2] Recently, the team of Benoit
Van den Eynde (LICR, UCL, Belgium) has shown that tryptophan
2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing
the first step of tryptophan degradation, is also expressed in
many tumors and that this expression prevents tumor rejection by
locally depleting tryptophan.[3] In this communication, a detailed
structure–activity study of a series of 3-(2-(pyridyl)ethenyl)indoles
as TDO inhibitors will be presented. This study led to the identification
of a potent and orally available TDO inhibitor (LM10) that,
upon systemic treatment, restored the ability of mice to reject TDOexpressing
tumors. Our results thus describe a new mechanism of
tumoral immune resistance based on TDO expression and establish
proof-of-concept for the use of TDO inhibitors in cancer therapy.[4,5]
| langue originale | Anglais |
|---|---|
| Pages (de - à) | 371 |
| Nombre de pages | 1 |
| journal | ChemMedChem |
| état | Publié - 2012 |
Citer ceci
}
Reversal of Tumoral Immune Resistance by Inhibition of Tryptophan 2,3-Dioxygenase (TDO): Design, Synthesis and Preclinical Evaluation of a Novel TDO Inhibitor. / Dolušić, Eduard; Larrieu, Pierre; Moineaux, Laurence; Stroobant, Vincent; Pilotte, Luc; Colaux, Didier; Van den Eynde, Benoît; Masereel, Bernard; Wouters, Johan; Frédérick, Raphaël.
Dans: ChemMedChem, 2012, p. 371.Résultats de recherche: Contribution à un journal/une revue › Revue de documentation
TY - JOUR
T1 - Reversal of Tumoral Immune Resistance by Inhibition of Tryptophan 2,3-Dioxygenase (TDO): Design, Synthesis and Preclinical Evaluation of a Novel TDO Inhibitor.
AU - Dolušić, Eduard
AU - Larrieu, Pierre
AU - Moineaux, Laurence
AU - Stroobant, Vincent
AU - Pilotte, Luc
AU - Colaux, Didier
AU - Van den Eynde, Benoît
AU - Masereel, Bernard
AU - Wouters, Johan
AU - Frédérick, Raphaël
PY - 2012
Y1 - 2012
N2 - Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase(IDO1) is an important mechanism of peripheral immune tolerancecontributing to tumoral immune resistance,[1] and IDO1 inhibition isan active area of drug development.[2] Recently, the team of BenoitVan den Eynde (LICR, UCL, Belgium) has shown that tryptophan2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzingthe first step of tryptophan degradation, is also expressed inmany tumors and that this expression prevents tumor rejection bylocally depleting tryptophan.[3] In this communication, a detailedstructure–activity study of a series of 3-(2-(pyridyl)ethenyl)indolesas TDO inhibitors will be presented. This study led to the identificationof a potent and orally available TDO inhibitor (LM10) that,upon systemic treatment, restored the ability of mice to reject TDOexpressingtumors. Our results thus describe a new mechanism oftumoral immune resistance based on TDO expression and establishproof-of-concept for the use of TDO inhibitors in cancer therapy.[4,5]
AB - Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase(IDO1) is an important mechanism of peripheral immune tolerancecontributing to tumoral immune resistance,[1] and IDO1 inhibition isan active area of drug development.[2] Recently, the team of BenoitVan den Eynde (LICR, UCL, Belgium) has shown that tryptophan2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzingthe first step of tryptophan degradation, is also expressed inmany tumors and that this expression prevents tumor rejection bylocally depleting tryptophan.[3] In this communication, a detailedstructure–activity study of a series of 3-(2-(pyridyl)ethenyl)indolesas TDO inhibitors will be presented. This study led to the identificationof a potent and orally available TDO inhibitor (LM10) that,upon systemic treatment, restored the ability of mice to reject TDOexpressingtumors. Our results thus describe a new mechanism oftumoral immune resistance based on TDO expression and establishproof-of-concept for the use of TDO inhibitors in cancer therapy.[4,5]
M3 - Literature review
SP - 371
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
ER -