RVX-297

RVX-297 is a potent, orally active BET bromodomain inhibitor with selectivity for BD2. RVX-297 shows IC₅₀s of 0.08, 0.05, and 0.02 μM for BRD2(BD2), BRD3(BD2), and BRD4(BD2), respectively. RVX-297 suppresses inflammatory gene expression in multiple immune cell types. RVX-297 is effective in acute inflammation and autoimmunity models^[1][2]. In Vitro: RVX-297 (1-30 μM; 24 hours) decreases proinflammatory gene expression in synovial fibroblasts^[1].
RVX-297 displaces BET proteins from the promoters of sensitive genes and disrupted recruitment of active RNA polymerase II, a property shared with pan-BET inhibitors that nonselectively bind BET BDs^[1].
RVX-297 reduces gene expression of inflammatory mediators in vitro. RVX-297 suppresses IL-6 gene induction in human U937 macrophages, mouse primary B cells isolated from the spleen, mouse BMDMs, and THP-1 monocytes in a dose-dependent manner. RVX-297 represses IL-1β expression in LPS-stimulated mouse BMDMs, with an IC₅₀ of 0.4-3 μM. RVX-297 inhibits MCP-1 expression in unstimulated human PBMCs with an IC₅₀ of 0.4 μM. RVX-297 inhibits antigen stimulation of T cells and the induction of IL-17 expression^[1]. In Vivo: RVX-297 (25-75 mg/kg; p.o.; per day for 6 day) inhibits progression of pathology in the rat collagen-induced arthritis model^[1].
RVX-297 (75-150 mg/kg) inhibits progression of pathology in the mouse collagen-induced arthritis model^[1].
RVX-297 suppresses cytokine production in LPS-treated mice^[1].