RN486 |
| Katalog-Nr.GC11230 |
RN486 ist ein potenter, selektiver und oral aktiver Btk-Inhibitor mit einem IC50 von 4,0 nM und einem Kd von 0,31 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1242156-23-5
Sample solution is provided at 25 µL, 10mM.
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RN486 is a reversible inhibitor of Btk with IC50 value of 4.0 nM [1].
Bruton's tyrosine kinase (Btk) is a type of kinase protein which is expressed by immune system-related cells (B-lymphocyte, monocytes, macrophages, neutrophils and mast cells) and plays a pivotal role in cell differentiation and proliferation at the transition from pre-B to later B cell stages as well as in the process of both BCR and FcR signaling [2]. It has been reported that aberrant BCR signaling is associated with autoimmune diseases, for example, rheumatoid arthritis (RA) [3].
RN486 is a selective Btk inhibitor. When tested with human Ramos B cells or whole blood, RN486 treatment reduced the expression of CD69/B cells proliferation and IgG production by blocking BCR and FcR Signaling [1].
In NZB × NZW mouse model with systemic lupus erythematosus (SLE), compared with control group, RN486 treatment completely stopped disease progression by inhibiting BTK signaling and targeting other autoantibody-producing and effector cells [4]. In a PCA (type I hypersensitivity) mouse model or rPCA (type III hypersensitivity) mouse model, RN486 treatment significantly inhibited inflammatory response. In mouse model of RA, administration of RN486 orally could reduce both paw swelling and inflammatory markers in the blood by inhibiting both joint and systemic inflammation alone or in combination with methotrexate [1].
RN486 may also play a pivotal role in reducing immune complex-mediated activation of human monocytes and down-regulating the expression of macrophage-related and interferon-inducible genes [4].
References:
[1]. Xu, D., et al., RN486, a selective Bruton's tyrosine kinase inhibitor, abrogates immune hypersensitivity responses and arthritis in rodents. J Pharmacol Exp Ther, 2012. 341(1): p. 90-103.
[2]. Kil, L.P., et al., Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice. Blood, 2012. 119(16): p. 3744-56.
[3]. Hartkamp, L.M., et al., Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants. Ann Rheum Dis, 2014.
[4]. Mina-Osorio, P., et al., Suppression of glomerulonephritis in lupus-prone NZB x NZW mice by RN486, a selective inhibitor of Bruton's tyrosine kinase. Arthritis Rheum, 2013. 65(9): p. 2380-91.
| Cas No. | 1242156-23-5 | SDF | |
| Chemical Name | 6-cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)pyridin-2-yl]amino]-6-oxopyridin-3-yl]phenyl]isoquinolin-1-one | ||
| Canonical SMILES | CN1CCN(CC1)C2=CN=C(C=C2)NC3=CC(=CN(C3=O)C)C4=C(C(=CC=C4)N5C=CC6=CC(=CC(=C6C5=O)F)C7CC7)CO | ||
| Formula | C35H35FN6O3 | M.Wt | 606.69 |
| Löslichkeit | ≥ 30.35mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6483 mL | 8.2414 mL | 16.4829 mL |
| 5 mM | 329.7 μL | 1.6483 mL | 3.2966 mL |
| 10 mM | 164.8 μL | 824.1 μL | 1.6483 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)
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