Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction.

ABSTRACT: Costimulatory interactions are required for T cell activation and development of an effective immune response; hence, they are valuable therapeutic targets for immunomodulation. However, they, as all other protein-protein interactions, are difficult to target by small molecules. Here, we report the identification of novel small-molecule inhibitors of the CD40-CD40L interaction designed starting from the chemical space of organic dyes. For the most promising compounds such as DRI-C21045, activity (IC₅₀) in the low micromolar range has been confirmed in cell assays including inhibition of CD40L-induced activation in NF-κB sensor cells, THP-1 myeloid cells, and primary human B cells as well as in murine allogeneic skin transplant and alloantigen-induced T cell expansion in draining

SUBMITTER: Chen J 

PROVIDER: S-EPMC5823691 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature