What question did this study set out to answer?

The aim is to identify small molecule modulators of the TL1A/DR3 signaling pathway associated with inflammation.

May 8, 2026Open Access

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

Key Points

The aim is to identify small molecule modulators of the TL1A/DR3 signaling pathway associated with inflammation.
Conducted a cell-based high throughput screen of 8,000 compounds.
Focused on identifying modulators of the TL1A/DR3 pathway.
Assessed the expression of inflammation-promoting gene products.
Identified 12 antagonists but no agonists of the TL1A/DR3 pathway.
Antagonists indicated potential for modifying inflammation in autoimmune diseases.
No significant modulators were found among the screened compounds.

Abstract

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-B-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.

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Cite This Study

Smith et al. (Fri,) studied this question.

synapsesocial.com/papers/69fd7ddcbfa21ec5bbf06063 https://doi.org/https://doi.org/10.1016/j.slasd.2026.100312

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