Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction.

ABSTRACT:

Background and purpose

The OX40-OX40L protein-protein interaction (PPI) is an important cell-surface signalling co-stimulatory regulator within the TNFR superfamily (TNFRSF) and a promising therapeutic target for immunomodulation. PPIs are difficult to modulate using small-molecules. Here, we describe the identification of a small-molecule OX40 modulator and confirm its partial agonist character.

Experimental approach

Cell-free screening assays were developed and used to identify OX40-OX40L inhibitors. Modified versions of this assay were used to elucidate the binding partner and the binding nature of active compounds. OX40-transfected sensor cells with NF-κB reporters were constructed and used to confirm and characterize activity and specificity. Immunomodulatory activity a

SUBMITTER: Song Y 

PROVIDER: S-EPMC4294117 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature