公开(公告)号：EP3154536A1

公开(公告)日：2017-04-19

申请号：EP15731531.8

申请日：2015-06-09

申请人： Institut National de la Santé et de la Recherche Médicale (INSERM) ,  Fondation Imagine ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Université Paris Descartes ,  Centre National de la Recherche Scientifique (C.N.R.S.)

发明人： HERMINE, Olivier ,  ARLET, Jean-Benoit ,  GUILLEM, Flavia ,  COURTOIS, Genevève ,  FONTENAY, Michaela

IPC分类号： A61K31/165 ,  A61P35/02

CPC分类号： A61K31/422 ,  A61K31/00 ,  A61K31/366

摘要： The present invention provides methods and pharmaceutical compositions designed to intervene in this defective process and to promote or restore erythrocyte maturation in individuals suffering from a myelodysplastic syndrome. The methods involve maintaining the activity of GATA-1 by preventing sequestration of Hsp70 in the cytoplasm. Accordingly, it is an object of this invention to provide methods of restoring or increasing erythrocyte maturation in a subject suffering from a myelodysplastic syndrome by preventing proteolytic inactivation of GATA-1. In some embodiments, preventing is achieved by administering to the subject a compound that inhibits the XPO1 nuclear transporter.

摘要翻译： 本发明提供了设计用于干预该缺陷过程并促进或恢复患有骨髓增生异常综合征的个体的红细胞成熟的方法和药物组合物。 该方法涉及通过防止细胞质中Hsp70的螯合来维持GATA-1的活性。 因此，本发明的目的是通过预防GATA-1的蛋白水解失活来提供恢复或增加患有骨髓增生异常综合征的受试者的红细胞成熟的方法。 在一些实施方案中，通过向受试者施用抑制XPO1核转运蛋白的化合物来实现预防。