Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy
| Autor: | Dolusic, Eduard, Blanc, Sébastien, Larrieu, Pierre, Moineaux, Laurence, Colette, Delphine, Fraser, Graeme, Stroobant, Vincent, Pilotte, Luc, Colau, Didier, Wouters, Johan, Masereel, Bernard, Van den Eynde, Benoît, Frédérick, Raphaël |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Zdroj: | Dolusic, E, Blanc, S, Larrieu, P, Moineaux, L, Colette, D, Fraser, G, Stroobant, V, Pilotte, L, Colau, D, Wouters, J, Masereel, B, Van den Eynde, B & Frédérick, R 2011, ' Novel Inhibitors of Indoleamine 2,3-Dioxygenase (IDO), a Target for Anti-Cancer Immunotherapy ', XVIIIeme JOURNEE JEUNES CHERCHEURS, Paris, Faculte de Pharmacie, France, 4/02/11 pp. Book of Abstracts, XVIIIème Journée Jeunes Chercheurs, 04/02/11, Paris, France . |
| Popis: | Anti-cancer vaccination has so far shown a limited efficacy because cancer cells develop mechanisms of resisting or escaping immune rejection. The enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the oxidative degradation of tryptophan, has been identified as an important actor in this process. It has been demonstrated that many human tumors express IDO in a constitutive manner. [1] The recent elucidation of the three-dimensional structure of IDO [2] provides a basis for the structure-based drug discovery and design of IDO inhibitors. In the present work, [3] we applied virtual screening to discover new IDO inhibitors. The potency of the most promising candidate (1) was confirmed in vitro (IC50 = 65 µM) and could be improved 5-fold by pharmacomodulations. A number of analogs were also active in a cellular test. A modeling study was undertaken in order to explain the SAR. |
| Databáze: | OpenAIRE |
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