Use of tpp ii inhibitors in combination with...

A - Human Necessities – 61 – K

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A61K 38/06 (2006.01) A61N 5/10 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2636533

TPP II (tripeptidyl peptidase II) inhibitors are useful in enhancing the efficacy of gamma- irradiation cancer therapy or increasing the in vivo gamma- irradiation susceptibility of tumour cells. Suitable compounds comprise tripeptide compounds of general formula RN1RN2N-A1-A2-A3-CO-RC1 wherein RN1, RN2, A1, A2, A3 and RC1 are as defined herein, and which include for example the tripeptide sequences GLA and GPG. Complete in vivo tumor regression in mice injected with TPPII inhibitors is observed, during treatment in combination with gamma-irradiation.

La présente invention concerne des inhibiteurs de la tripeptidyle peptidase (TPP II) utiles pour l'amélioration de l'efficacité de la thérapie anticancéreuse par irradiation gamma ou l'accroissement in vivo de la susceptibilité de cellules tumorales à l'irradiation gamma. Des composés appropriés comprennent des composés de tripeptides de formule générale RN1RN2N-A1-A2-A3-CO-RC1 dans laquelle RN1, RN2, A1, A2, A3 et RC sont tels que définis dans la description, et qui comprennent par exemple les séquences tripeptidiques GLA et GPG. On a constaté une régression tumorale complète in vivo chez des souris injectées avec des inhibiteurs TPPII lors d'un traitement en combinaison avec l'irradiation gamma.

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