RN-486
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 PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/1896276
| Cas No. |
1242156-23-5 |
|---|---|
| Purity |
≥98% |
| Formula |
C35H35FN6O3 |
| Formula Wt. |
606.69 |
| IUPAC Name |
6-Cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-(1-methyl-5-{[5-(4-methyl-1-piperazinyl)-2-pyridinyl]amino}-6-oxo-1,6-dihydro-3-pyridinyl)phenyl]-1(2H)-isoquinolinone |
| Synonym |
RN486 |
| Appearance |
White to off white powder |
Zhao X, Huang W, Wang Y, et al. Discovery of novel Brutons 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. Brutons 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 Brutons tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103. PMID: 22228807.
