New SLC15A4-Targeting Compound Shows Early Promise in Treating Lupus

Scripps Research scientists have developed a compound that can block a protein (SLC15A4) previously considered challenging to drug and which is implicated in autoimmune diseases, including lupus.

Scientists from Scripps Research have developed a small molecule that blocks the activity of a protein linked to autoimmune diseases, including systemic lupus erythematosus (SLE) and Crohn’s disease. This protein, known as SLC15A4, has been considered largely “undruggable,” as most researchers had long struggled to isolate the protein, determine its structure, or even pin down its exact function within immune cells—until now. The new research, published in Nature Chemical Biology on January 8, 2024, shows that the blocking compound successfully reduced inflammation in mouse models of inflammation, as well as in isolated cells from people diagnosed with lupus. This provides scientists with a new tool to study the role of SLC15A4 in autoimmunity, as well as a potential new therapy to move toward additional preclinical trials. The article is titled “Chemoproteomic Development of SLC15A4 Inhibitors with Anti-Inflammatory Activity.”

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