GSK761 (GSK-761) is the first small molecule inhibitor of bromodomain-containing protein SP140, inhibits macrophage inflammatory function.
GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation in macrophages.
GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes.
GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from Crohn's disease (CD) intestinal mucosa.
SP140 is a bromodomain-containing protein expressed predominantly in immune cells.
SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways.
