公开(公告)号：EP2137536B1

公开(公告)日：2015-03-04

申请号：EP08744408.9

申请日：2008-03-26

申请人： University Of Southern California, USC Stevens

发明人： SCHONTHAL, Axel, H. ,  PETASIS, Nicos, A. ,  HOFMAN, Florence, M. ,  LOUIE, Stan, G. ,  CHEN, Thomas, C.

IPC分类号： G01N33/574 ,  C12N5/00 ,  A61P35/00 ,  A61K31/415 ,  C12N5/09 ,  G01N33/50

CPC分类号： A61K31/635 ,  A61K31/415 ,  A61K31/4188 ,  A61K38/005 ,  A61K38/05 ,  A61N5/10 ,  C12N5/0693 ,  C12N5/0694 ,  C12N2501/48 ,  G01N33/5076 ,  G01N2333/90245 ,  G01N2333/914 ,  G01N2510/00

公开(公告)号：EP2137536A1

公开(公告)日：2009-12-30

申请号：EP08744408.9

申请日：2008-03-26

申请人： University Of Southern California USC Stevens

发明人： SCHONTHAL, Axel, H. ,  PETASIS, Nicos, A. ,  HOFMAN, Florence, M. ,  LOUIE, Stan, G. ,  CHEN, Thomas, C.

IPC分类号： G01N33/574 ,  C12N5/00

CPC分类号： A61K31/635 ,  A61K31/415 ,  A61K31/4188 ,  A61K38/005 ,  A61K38/05 ,  A61N5/10 ,  C12N5/0693 ,  C12N5/0694 ,  C12N2501/48 ,  G01N33/5076 ,  G01N2333/90245 ,  G01N2333/914 ,  G01N2510/00

摘要： The present invention provides a method for inducing apoptosis in selected cells by aggravating ER-stress. The aggravation of ER-stress is achieved in a specific manner by inhibiting SERCA (sarcoplasmic/endoplasmic reticulum calcium ATPase), leading to elevated level of cytoplasmic calcium concentration, yet without inhibiting the activity of COX-2 (cyclooxygenase-2) or triggering the release of histamine. Induction of apoptosis may be enhanced by first inducing or further aggravating ER-stress through inhibition of proteasome or proteases. Also provided are compounds and compositions useful as ER-stress aggravating agents, methods for screening, selecting, identifying and designing the same and methods for treating diseased conditions by inducing apoptosis through specific and selective aggravation of ER-stress.