RVX-297 (C09-1167-418)

RVX-297 is a potent, orally active BET bromodomain inhibitor with selectivity for BD2. RVX-297 shows IC 50 s 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.In VitroRVX-297 (1-30 μM; 24 hours) decreases proinflammatory gene expression in synovial fibroblasts. 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. 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 IC 50 of 0.4-3 μM. RVX-297 inhibits MCP-1 expression in unstimulated human PBMCs with an IC 50 of 0.4 μM. RVX-297 inhibits antigen stimulation of T cells and the induction of IL-17 expression. MCE has not independently confirmed the accuracy of these methods. They are for reference only. RT-PCRCell Line: Synovial fibroblasts Concentration: 1-30 μM Incubation Time: 24 hours Result: Downregulated IL-6 and VCAM-1 gene expression in synovial fibroblasts.In VivoRVX-297 (25-75 mg/kg; p.o.; per day for 6 day) inhibits progression of pathology in the rat collagen-induced arthritis model . RVX-297 (75-150 mg/kg) inhibits progression of pathology in the mouse collagen-induced arthritis model . RVX-297 suppresses cytokine production in LPS-treated mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female Lewis rats are 6-8 weeks old, approximately 150 g (rat collagen-induced arthritis) Dosage: 25, 50, and 75 mg/kg Administration: P.o.; per day for 6 days Result: Prevented swelling and inflammation of the ankle and knee joints.Form:Solid. Specification: 0.96 Molecular Formula: C24H29N3O4 Molecular Weight: 423.5 PubChem CID: 135567084 Isomeric SMILES: CC1=CC(=CC(=C1OCCN2CCCC2)C)C3=NC4=C(C(=CC(=C4)OC)OC)C(=O)N3