Work

BRD3 PROTAC degrader targets H3K18ac to alleviate retinal microglia-driven uveitis

Year: 2025

Type: article

Abstract: and inhibited proinflammatory microglia in both uveitis retina and lipopolysaccharide (LPS) treated mouse microglia cell line BV2. Drug target verification revealed that D072 specifically degraded BRD3 but did not significantly affect BRD2 or BRD4. Mechanistically, BRD3 degradation resulted in reduced H3K18ac, and CUT&Tag analysis revealed changes in the occupancy of several proinflammatory and metabolism-related genes. Furthermore, histone deacetylases (HDACs) partially regulate the H3K18ac level following BRD3 degradation. Overall, we identified D072 as a specific degrader of BRD3 in the murine system that can inhibit proinflammatory microglia in autoimmune uveitis, potentially providing a therapeutic approach for uveitis.

Source: iScience

DOI: 10.1016/j.isci.2025.114526