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RN486
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
RN486图片
CAS NO:1242156-23-5
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)606.69
FormulaC35H35FN6O3
CAS No.1242156-23-5
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 62 mg/mL (102.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)5% DMSO+30% PEG 300+10% Tween 80+ddH2O: 5mg/mL
SynonymsRN-486; RN 486; RN486;

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

实验参考方法
In Vitro

In vitro activity: RN486 not only potently and selectively inhibits the Btk enzyme, but also displays functional activities in human cell-based assays in multiple cell types, blocking Fcε receptor cross-linking-induced degranulation in mast cells (IC50 = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC50 = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC50 = 21.0 nM). RN486 is able to block the signaling of BCR as demonstrated by a marked inhibition of phosphorylation of both Btk and PLCγ2 in B cells. RN486 displays a selective B cell inhibitory profile in BioMAP Systems.


Kinase Assay: RN486 is a novel, potent and selective BTK inhibitor with IC50 of 4 nM. 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).


Cell Assay: In a co-culture system consisting of human primary synovial FLS and activated human platelets, convulxin stimulation resulted in elevated production of pro-inflammatory cytokines, IL-6 and IL-8, an effect which was dose-dependently blocked by RN486.

In VivoRN486 displays similar functional activities in rodent models, effectively preventing type I and type III hypersensitivity responses. More importantly, RN486 produces robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 inhibits both joint and systemic inflammation either alone or in combination with methotrexate, reducing both paw swelling and inflammatory markers in the blood.
Animal modelRodent models
Formulation & DosageN/A
ReferencesJ Pharmacol Exp Ther. 2012 Apr;341(1):90-103.
生物活性


Inhibitory effect of RN486 on the effector phase of immune arthritis in mice. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103.



Anti-inflammatory and disease-modifying effects of RN486 in the rat AIA model. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103.


Additive inhibitory effects of RN486 and MTX on inflammation and bone erosions in the rat AIA model. J Pharmacol Exp Ther. 2012 Apr;341(1):90-103.