WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406103
CAS#: 1242156-23-5
Description: RN486 is a Bruton's tyrosine kinase (Btk) inhibitor. RN486 not only potently and selectively inhibited the Btk enzyme, but also displayed functional activities in human cell-based assays in multiple cell types, blocking Fcε receptor cross-linking-induced degranulation in mast cells (IC(50) = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC(50) = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC(50) = 21.0 nM).
Hodoodo Cat#: H406103
Name: RN486
CAS#: 1242156-23-5
Chemical Formula: C35H35FN6O3
Exact Mass: 606.28
Molecular Weight: 606.690
Elemental Analysis: C, 69.29; H, 5.81; F, 3.13; N, 13.85; O, 7.91
Synonym: RN486; RN-486; RN 486
IUPAC/Chemical Name: 6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one
InChi Key: ZTUJNJAKTLHBEX-UHFFFAOYSA-N
InChi Code: InChI=1S/C35H35FN6O3/c1-39-12-14-41(15-13-39)26-8-9-32(37-19-26)38-30-18-25(20-40(2)34(30)44)27-4-3-5-31(28(27)21-43)42-11-10-23-16-24(22-6-7-22)17-29(36)33(23)35(42)45/h3-5,8-11,16-20,22,43H,6-7,12-15,21H2,1-2H3,(H,37,38)
SMILES Code: O=C1N(C2=CC=CC(C(C=C3NC4=NC=C(N5CCN(C)CC5)C=C4)=CN(C)C3=O)=C2CO)C=CC6=C1C(F)=CC(C7CC7)=C6
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO and DMF
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO and DMF
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | |
| In vitro activity: | |
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The following data is based on the product molecular weight 606.69 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Mina-Osorio P, LaStant J, Keirstead N, Whittard T, Ayala J, Stefanova S, Garrido R, Dimaano N, Hilton H, Giron M, Lau KY, Hang J, Postelnek J, Kim Y, Min S, Patel A, Woods J, Ramanujam M, DeMartino J, Narula S, Xu D. Suppression of glomerulonephritis in lupus-prone NZB × NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum. 2013 Sep;65(9):2380-91. doi: 10.1002/art.38047. PubMed PMID: 23754328.
2: Xu D, Kim Y, Postelnek J, Vu MD, Hu DQ, Liao C, Bradshaw M, Hsu J, Zhang J, Pashine A, Srinivasan D, Woods J, Levin A, O'Mahony A, Owens TD, Lou Y, Hill RJ, Narula S, DeMartino J, Fine JS. 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. doi: 10.1124/jpet.111.187740. PubMed PMID: 22228807.
3: Lou Y, Han X, Kuglstatter A, Kondru RK, Sweeney ZK, Soth M, McIntosh J, Litman R, Suh J, Kocer B, Davis D, Park J, Frauchiger S, Dewdney N, Zecic H, Taygerly JP, Sarma K, Hong J, Hill RJ, Gabriel T, Goldstein DM, Owens TD. Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis. J Med Chem. 2015 Jan 8;58(1):512-6. doi: 10.1021/jm500305p. PubMed PMID: 24712864.
4: Hartkamp LM, Fine JS, van Es IE, Tang MW, Smith M, Woods J, Narula S, DeMartino J, Tak PP, Reedquist KA. Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants. Ann Rheum Dis. 2015 Aug;74(8):1603-11. doi: 10.1136/annrheumdis-2013-204143. PubMed PMID: 24764451.
5: Zhao X, Huang W, Wang Y, Xin M, Jin Q, Cai J, Tang F, Zhao Y, Xiang H. 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. doi: 10.1016/j.bmc.2014.10.043. PubMed PMID: 25596757.
6: Zhao X, Xin M, Huang W, Ren Y, Jin Q, Tang F, Jiang H, Wang Y, Yang J, Mo S, Xiang H. Design, synthesis and evaluation of novel 5-phenylpyridin-2(1H)-one derivatives as potent reversible Bruton's tyrosine kinase inhibitors. Bioorg Med Chem. 2015 Jan 15;23(2):348-64. doi: 10.1016/j.bmc.2014.11.006. PubMed PMID: 25515957.
7: Hsu J, Gu Y, Tan SL, Narula S, DeMartino JA, Liao C. Bruton's Tyrosine Kinase mediates platelet receptor-induced generation of microparticles: a potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints. Immunol Lett. 2013 Feb;150(1-2):97-104. doi: 10.1016/j.imlet.2012.12.007. PubMed PMID: 23266841.
8: Wang J, Lau KY, Jung J, Ravindran P, Barrat FJ. Bruton's tyrosine kinase regulates TLR9 but not TLR7 signaling in human plasmacytoid dendritic cells. Eur J Immunol. 2014 Apr;44(4):1130-6. doi: 10.1002/eji.201344030. PubMed PMID: 24375473.
9: Zhao X, Huang W, Wang Y, Xin M, Jin Q, Cai J, Tang F, Zhao Y, Xiang H. Pyrrolo[2,3-b]pyridine derivatives as potent Bruton's tyrosine kinase inhibitors. Bioorg Med Chem. 2015 Aug 1;23(15):4344-53. doi: 10.1016/j.bmc.2015.06.023. PubMed PMID: 26169764.
