Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40⁻CD154 Costimulatory Protein-Protein Interaction.

ABSTRACT: We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules. Following up on our previous work, we have now identified novel compounds such as DRI-C21091 or DRI-C21095 that show activity (IC₅₀) in the high nanomolar to low micromolar range in the binding inhibition assay and more than thirty-fol

SUBMITTER: Bojadzic D 

PROVIDER: S-EPMC5978685 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature