Synthèse et évaluation de dérivés hétérocycliques 1-H-indol-3-yl comme inhibiteurs de la tryptophane 2,3-dioxygénase

Details

Supervisors

Frédérick, Raphaël

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences pharmaceutiques

Abstract

enImmunotherapy is a therapeutic approach increasingly used to treat cancer. The principle is to activate our own immune system to fight the tumor. This type of treatment often involves multitherapy because despite its effectiveness, some patients show resistance. One of the approaches chosen is to combine these treatments with small molecules that activate the immune system. TDO2 and IDO1 are two enzymes involved in the metabolism of Trp, an essential amino acid. They catalyze the first reaction of the kynurenin pathway, which is the oxidative cleavage of L-Trp into N-formylkynurenin. At the pathological level, theseenzymes are (co-)expressed in about 50% of human tumors. They participate in the escape of tumors from the immune system by the decrease of Trp and the increase of Kyn in the tumor microenvironment, which causes an anergy of effector T-cells and a shift towards a tolerogenic phenotype of antigen presenting cells. In fact, a mouse model has proven that inhibiting TDO can reduce tumor development. In this master thesis, we will focus on an TDO inhibitor synthesis in the context of the research against cancer.