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].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD2 (BD1):3.76 μM (IC50)

BRD2 (BD2):0.08 μM (IC50)

BRD3 (BD1):2.34 μM (IC50)

BRD3 (BD2):0.05 μM (IC50)

BRD4 (BD1):1.16 μM (IC50)

BRD4 (BD2):0.02 μM (IC50)

BRDT (BD1):2.69 μM (IC50)

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]. RT-PCR[1] Cell Line: Synovial fibroblasts Concentration: 1-30 μM Incubation Time: 24 hours Result: Downregulated IL-6 and VCAM-1 gene expression in synovial fibroblasts.

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]. Animal Model: Female Lewis rats are 6-8 weeks old, approximately 150 g (rat collagen-induced arthritis)[1] 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.

[1]. Jahagirdar R, et al. RVX-297, a BET Bromodomain Inhibitor, Has Therapeutic Effects in Preclinical Models of Acute Inflammation and Autoimmune Disease. Mol Pharmacol. 2017;92(6):694-706.

[2]. Kharenko OA, et al. RVX-297- a novel BD2 selective inhibitor of BET bromodomains. Biochem Biophys Res Commun. 2016;477(1):62-67.