Author/Authors :
Jianming Bao، نويسنده , , ShouWu Miao، نويسنده , , Frank Kayser، نويسنده , , Andrew J. Kotliar، نويسنده , , Robert K. Baker، نويسنده , , George A. Doss، نويسنده , , John P. Felix، نويسنده , , Randal M. Bugianesi، نويسنده , , Robert S. Slaughter، نويسنده , , Gregory J. Kaczorowski، نويسنده , , Maria L. Garcia، نويسنده , , Sookhee N. Ha، نويسنده , , Laurie Castonguay، نويسنده , , Gloria C. Koo، نويسنده , , Kashmira Shah، نويسنده , , Marty S. Springer، نويسنده , , Mary Jo Staruch، نويسنده , , William H. Parsons، نويسنده , , Kathleen M. Rupprecht، نويسنده ,
Abstract :
Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure–activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation.
Keywords :
Potassium channel , Correolide , Kv1.3 , Ion channel blocker , T cell , Immunosuppressant
