A High Throughput Assay to Identify Modulators of Death Receptor 3 (DR3)

Association of the TNF-like cytokine 1A (TL1A) with Death Receptor 3 (DR3) triggers a signaling cascade in T cells that results in the increased AP-1- and NF-κB-mediated expression of inflammation-promoting gene products. Dysregulation of TL1A/DR3 signaling is a major contributor to many autoimmune diseases, cancers, and other conditions yet there is a dearth of small molecule regulators of this pathway. Here we report a cell-based high throughput screen of 8,000 compounds of compounds that yielded 12 antagonists but no agonists of this pathway.