%0 Journal Article
%T Selective Inhibitors of T Cell Receptor Recognition of Antigen¨CMHC Complexes for Rheumatoid Arthritis
%J -
%D 2019
%R https://doi.org/10.1021/acsmedchemlett.8b00601
%X Autoreactive T cells specific to human collagen type II have a crucial role in the development of rheumatoid arthritis (RA) in the context of MHC class II allele HLA-DRB1-*04. The protein¨Cprotein interactions between the T cell receptor (TCR) and the type II collagen bound to the allele MHC of class II may thus represent the target for the development of new drugs against RA. In this study, a structure-based pharmacophore model for potential small molecule inhibitors was developed from protein¨Cprotein interface structure. The 3D model obtained was used for a virtual screening workflow, which resulted in three hits for experimental follow up. Three compounds have been identified that interfere with the TCR/collagenII-MHCII (Ki values below 10 ¦ÌM) and open up new possibilities in the treatment of RA
%U https://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00601