公开(公告)号：US20220307021A1

公开(公告)日：2022-09-29

申请号：US17614437

申请日：2020-06-03

申请人： INSERM (Institut National de la santé et de la Recherche Médicale) ,  Université de Paris ,  Centre National de la Recherche Scientifique (CNRS) ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Fondation Imagine ,  Conservatoire National des Arts et Métiers (CNAM)

发明人： Yves LEPELLETIER ,  Matthieu MONTES ,  Luc DEMANGE ,  François RAYNAUD ,  Rachel RIGNAULT-BRICARD ,  Olivier HERMINE ,  Nicolas LOPEZ

IPC分类号： C12N15/113 ,  A61P35/00 ,  C07K16/28

摘要： Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. More importantly, the association of NRPa with a p38α inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38α-kinase inhibitors are thus credible for the treatment of cancer.