Description
RN-486 is an inhibitor of Bruton’s tyrosine kinase (Btk) that is currently in development as a potential treatment for rheumatoid arthritis; it exhibits anti-inflammatory, nephroprotective, and immunosuppressive activities. RN-486 decreases production of IL-6 and expression of IL-8, TNF, MMP1, and MMP10 in synovial tissue. In animal models of systemic lupus erythmatosus (SLE), RN-486 inhibits B-cell activation and anti-double-stranded DNA IgG production, suppressing progression of glomerulonephritis. In other animal models, this compound inhibits mast cell degranulation, preventing type I and III hypersensitivity responses and limiting joint and systemic inflammation. RN-486 also decreases TLR-9 signaling and cytokine production.
References
Zhao X, Huang W, Wang Y, et al. Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold. Bioorg Med Chem. 2015 Feb 15;23(4):891-901. PMID: 25596757.
Hartkamp LM, Fine JS, van Es IE, et al. Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants. Ann Rheum Dis. 2014 Apr 24. [Epub ahead of print]. PMID: 24764451.
Wang J, Lau KY, Jung J, et al. Bruton's tyrosine kinase regulates TLR9 but not TLR7 signaling in human plasmacytoid dendritic cells. Eur J Immunol. 2014 Apr;44(4):1130-6. PMID: 24375473.
Xu D, Kim Y, Postelnek J, et al. RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. PMID: 22228807.
