公开(公告)号：US20190247416A1

公开(公告)日：2019-08-15

申请号：US16330956

申请日：2017-09-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  FONDATION IMAGINE ,  UNIVERSITE PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITE DE CAEN NORMANDIE ,  CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE CAEN

发明人： Olivier HERMINE ,  Flavia GUILLEM ,  Gandhi DAMAJ ,  Sophia LADRAA

IPC分类号： A61K31/7105 ,  A61K31/497

CPC分类号： A61K31/7105 ,  A61K31/497 ,  A61K31/713 ,  A61P35/00 ,  A61P35/04 ,  C12N15/00 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/531

摘要： The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA Δ 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

公开(公告)号：US20210308106A1

公开(公告)日：2021-10-07

申请号：US17324690

申请日：2021-05-19

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  FONDATION IMAGINE ,  UNIVERSITE PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITE DE CAEN NORMANDIE ,  CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE CAEN

发明人： Olivier HERMINE ,  Flavia GUILLEM ,  Gandhi DAMAJ ,  Sophia LADRAA

IPC分类号： A61K31/4196 ,  A61K31/506 ,  A61P37/00 ,  A61K31/397 ,  A61K31/4245

摘要： The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations: ROSA Δ 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.