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Filgotinib(GLPG-0634)
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。
Filgotinib(GLPG-0634)图片
CAS NO:1206161-97-8
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)425.50
FormulaC21H23N5O3S
CAS No.1206101-20-3 (GLPG0634 analogue); 1206161-97-8; 1206101-20-3;
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 85 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)4% DMSO+30% PEG 300+ddH2O: 3mg/mL
Synonyms

GLPG-0634; PubChemSID 163643231; GLPG0634; GLPG 0634; Filgotinib

Chemical Name: N-(5-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide.

SMILES Code: O=C(C1CC1)NC2=NN3C(C4=CC=C(CN5CCS(CC5)(=O)=O)C=C4)=CC=CC3=N2

实验参考方法
In Vitro

In vitro activity: In cell lines, GLPG0634 inhibits IL-2- and IL-4-induced JAK1/JAK3/γc signaling and IFN-αB2-induced JAK1/TYK2 type II receptor signaling with IC50 ranged from 150 to 760 nM. GLPG0634 shows higher selectivity for JAK/STAT signaling involving JAK1 than JAK2 kinase in a cellular context. Besides, GLPG0634 also inhibits the differentiation of Th1, Th2, and Th17 cells.


Kinase Assay: Recombinant JAK1, TYK2, JAK2, and JAK3 are used to develop activity assays in 50 mM HEPES (pH 7.5), 1 mM EGTA, 10 mM MgCl2, 2 mM DTT, and 0.01% Tween 20. The amount of JAK protein is determined per aliquot, maintaining initial velocity and linearity over time. The ATP concentration is equivalent to 4× the experimental Km value and the substrate concentration (ULight-conjugated JAK-1(Tyr1023) peptide) corresponds to the experimentally determined Km value. After 90 min incubation at room temperature (RT), the amount of phosphorylated substrate is measured by addition of 2 nM europium-anti-phosphotyrosine Ab and 10 mM EDTA in Lance detection buffer. Compound IC50 values are determined by preincubating the enzyme with compound at RT for 60 min, prior to the addition of ATP.


Cell Assay: GLPG0634 (50 mg/kg, o.p.) protects bone and cartilage from degradation, effectively reduces infiltration of T cells (CD3+ cells) and macrophages (F4/80+ cells) in the paw, and decreases the serum levels of all cytokines and chemokines measured, including IL-6, IP-10, XCL1, and MCP-1.

In VivoFollowing oral administration, the absolute bioavailability is moderate in rats (45%) and high in mice (~100%). Filgotinib (30 mg/kg daily (Rats); 50 mg/kg twice daily (Mice)) dose-dependently reduces inflammation, cartilage, and bone degradation in the CIA model in rats and mice. Filgotinib (GLPG0634) in DSS-treated mice demonstrates that inhibition of JAK1 is sufficient for achieving strong efficacy in pre-clinical mouse model, correlated to the inhibition of STAT3 phosphorylation in the inflamed colon.
Animal modelIn the rat model of collagen-induced arthritis (CIA), oral administration of GLPG0634 shows a marked protection from bone damage at dose of 3 mg/kg. It reduces the infiltration of inflammatory cells significantly from 1 mg/kg onward
Formulation & Dosage 30 mg/kg daily in Rats); 50 mg/kg twice daily in Mice
ReferencesJ Immunol. 2013 Oct 1;191(7):3568-77.
生物活性


GLPG0634 inhibits the differentiation of Th1, Th2, and Th17 cells. J Immunol.2013 Oct 1;191(7):3568-77.



GLPG0634 dose-dependently prevents disease progression in the therapeutic rat CIA model. J Immunol. 2013 Oct 1;191(7):3568-77.


GLPG0634 is efficacious in a mouse therapeutic CIA model. J Immunol. 2013 Oct 1;191(7):3568-77.