Quadragenics
IBD
The innate inflammatory pathway plays a critical role in the initiation and chronicity of UC mucosal inflammation by activating cytokines, whose enhanced expression produce recruitment, hyperactivation of effector immune cells and disruption of the epithelial barrier. BRD4 is an essential transcriptional coactivator regulating pro-inflammatory cytokine expression.
Our extensive in vitro and in vivo data demonstrate that Inhibiting BRD4 blocks acute inflammation and other human diseases.
Recent work showing that oncostatin M (OSM), and its receptor, OSMR, are highly expressed in IBD, mediate with failure of anti-TNF therapy. We have demonstrated BRD4 is needed for OSM signaling to activate fibroblasts. These data indicate that BRD4 inhibitors will offer a superior therapeutic for inflammatory disorders, especially for anti-TNF-resistant patients.
Anti-inflammatory in acute colitis
BRD4 inhibitors block the innate inflammation associated with ulcerative colitis.
anti-remodeling
Selective BRD4 inhibitors interfere with the activaiton of subepithelial myofibroblasts