RN486
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
RN486是可逆的BTK抑制剂,其IC50值为4.0 nM[1]。
布鲁顿酪氨酸激酶(BTK)是由免疫系统相关细胞(B淋巴细胞、单核细胞、巨噬细胞、中性粒细胞和肥大细胞)表达的一类激酶蛋白,对前B细胞成熟的阶段以及BCR和TcR信号传导中的细胞分化和增殖起着关键作用[2]。据报道,异常BCR信号传导与自身免疫性疾病相关,如类风湿关节炎(RA)[3]。
RN486是BTK选择性抑制剂。在人B淋巴瘤细胞(RAMOS细胞)或全血中,给予RN486可以阻断BCR和FcR的信号传导,减少CD69表达、B淋巴细胞增殖以及IgG产生[1]。
在系统性红斑狼疮(SLE)的NZB×NZW小鼠模型中,与对照组相比,给予RN486可以抑制BTK信号传导以及靶向作用于其它自身抗体产生和效应细胞,完全阻止疾病进程[4]。在PCA(I型超敏反应)或rPCA(III型超敏反应)的小鼠模型中,RN486治疗显著抑制炎症反应。在类风湿性关节炎的小鼠模型中, RN486单独口服或与甲氨喋呤联合给药可以通过抑制关节和全身性炎症来减少足肿胀度以及血液中的炎症标记物[1]。
RN486在减少免疫复合体介导的人单核细胞激活以及下调巨噬细胞相关基因和干扰素诱导基因表达方面可能具有重要作用[4]。
参考文献:
[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
.Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 606.69 |
Cas No. | 1242156-23-5 |
Formula | C35H35FN6O3 |
Solubility | ≥30.35 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH |
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 |
SDF | Download SDF |
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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
质量控制和MSDS
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