公开(公告)号：US10723750B2

公开(公告)日：2020-07-28

申请号：US15775770

申请日：2016-11-14

申请人： La Jolla Institute for Allergy and Immunology ,  Universiteit Gent ,  VIB VZW

发明人： Dirk Zajonc ,  Serge Van Calenbergh ,  Dirk Elewaut ,  Joren Guillaume

IPC分类号： C07H15/04 ,  A61K47/65 ,  A61P37/04 ,  A61P31/12 ,  A61P35/00 ,  A61K31/7028 ,  A61K31/739 ,  C07H15/18 ,  C07H15/06

摘要： The compounds, compositions and methods provided herein antagonize, inhibit, decrease, reduce, suppress, or disrupt CD1d-mediated, iNKT cell-mediated, and/or iNKT cell TCR-mediated immune signaling. The sphingamide compounds were rationally designed based upon 3D structural considerations in relation to the structures of each of CD1d, the iNKT cell TCR, and the ternary complex CD1d-a-GalCer analog lipids-TCR. More specifically, the addition of an amide in the phytosphingosine tail of a derivative of α-GalCer led to a non-conserved binding with CD1d, a conserved binding with the iNKT cell TCR, and an antagonist-like phenotype.

公开(公告)号：US20190256541A1

公开(公告)日：2019-08-22

申请号：US15775770

申请日：2016-11-14

申请人： LA JOLLA INSTITUTE FOR ALLERGEY AND IMMUNOLOGY ,  UNIVERSITY OF GENT ,  VIB VZW

发明人： Dirk Zajonc ,  Serge Van Calenbergh ,  Dirk Elewaut ,  Joren Guillaume

IPC分类号： C07H15/04 ,  C07H15/18 ,  A61P31/12 ,  A61P35/00 ,  A61P37/04 ,  A61K47/65 ,  A61K31/7028 ,  A61K31/739

摘要： The compounds, compositions and methods provided herein antagonize, inhibit, decrease, reduce, suppress, or disrupt CD1d-mediated, iNKT cell-mediated, and/or iNKT cell TCR-mediated immune signaling. The sphingamide compounds were rationally designed based upon 3D structural considerations in relation to the structures of each of CD1d, the iNKT cell TCR, and the ternary complex CD1d-a-GalCer analog lipids-TCR. More specifically, the addition of an amide in the phytosphingosine tail of a derivative of α-GalCer led to a non-conserved binding with CD1d, a conserved binding with the iNKT cell TCR, and an antagonist-like phenotype.