GSK3358699

GSK3358699 is a small molecule inhibitor targeting the bromodomain and extra-terminal domain (BET) family, specifically designed to modulate mononuclear myeloid cells. It demonstrates immunomodulatory effects in vitro by inhibiting BET proteins, which are epigenetic reader proteins involved in regulating gene expression related to inflammation and immune responses. Developed by GSK, this compound was investigated for its potential as a transformative therapy for immuno-inflammatory diseases such as rheumatoid arthritis. In clinical studies, it showed significant inhibition of ex vivo lipopolysaccharide-induced monocyte chemoattractant protein-1 (MCP-1) but did not inhibit interleukin-6 or tumor necrosis factor production. The most common adverse event reported was headache; some cardiac-related adverse events were also observed, leading to study termination due to safety concerns[1][3][6].