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Filgotinib

Cat. No. M2346
Filgotinib Structure
Synonym:

GLPG0634

Size Price Availability Quantity
5mg USD 70 In stock
10mg USD 100 In stock
50mg USD 280 In stock
100mg USD 480 In stock
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Quality Control
Biological Activity

Filgotinib (GLPG0634) is an orally-available, selective inhibitor of JAK1 (Janus kinase 1) for the treatment of rheumatoid arthritis and potentially other inflammatory diseases. Filgotinib (GLPG0634) dose-dependently inhibited Th1 and Th2 differentiation and to a lesser extent the differentiation of Th17 cells in vitro. GLPG0634 was well exposed in rodents upon oral dosing, and exposure levels correlated with repression of Mx2 expression in leukocytes. The JAK1 selective inhibitor GLPG0634 (Filgotinib) is a promising novel therapeutic with potential for oral treatment of rheumatoid arthritis and possibly other immune-inflammatory diseases. Filgotinib (GLPG0634) is currently in a Phase 2 study in Crohn's disease.

Protocol
Cell Experiment
Cell lines T cells
Preparation method T cell differentiation studies. PBMCs were isolated from buffy coats of healthy donors (Blood Transfusion Center, Red Cross, Leuven, Belgium) using density gradient centrifugation on Lymphoprep. Naive CD4+ T cells were further isolated by depletion of non–T helper and memory CD4+ T cells using a naive CD4+ T cell isolation kit II (Miltenyi Biotec). Isolated naive CD4+ T cells were stimulated with plate-bound anti-CD3 (3 μg/ml) and anti-CD28 (5 μg/ml) Abs in the presence of cytokines that drive differentiation into Th1, Th2, or Th17 Th subsets. For Th1 cell polarization, cells were cultured in the presence of 10 μg/ml anti–IL-4 Ab (MAB204; R&D Systems), 10 ng/ml IL-2 (R&D Systems), and 10 ng/ml IL-12 (R&D Systems) (17). For Th2 cell polarization, cells were cultured in the presence of 10 μg/ml anti–IFN-γ Ab (Becton Dickinson), 25 ng/ml IL-4 (R&D Systems), and 10 ng/ml IL-2 (17). For Th17 cell polarization, a mix of the following cytokines was used: 10 ng/ml IL-6 (R&D Systems), 10 ng/ml IL-1β (R&D Systems), 1 ng/ml TGF-β (PeproTech), and 100 ng/ml IL-23 (R&D Systems) (18). To monitor effects of compounds on T cell differentiation, compounds were added at indicated concentrations at the start of T cell differentiation. After 5 d, RNA was extracted using an RNeasy Mini kit (Qiagen), reverse transcribed, and the extent of Th subset differentiation was monitored by determining expression of IFN-γ (Th1 marker), IL-13 (Th2 marker), or IL-17F (Th17 marker) using real-time PCR on the ViiA7 thermocycler with predesigned TaqMan Assay-on-Demand gene expression primer/probe sets (Applied Biosystems). Gene expression was normalized to 18S and expressed as ΔCt values, with ΔCt = Ctgene − Ct18S or expressed as relative mRNA level of specific gene expression as obtained using the 2−ΔCt method.
Concentrations 10, 1, 0.1 or 0 μM
Incubation time 5 days
Animal Experiment
Animal models therapeutic rat CIA model
Formulation 0.05 M acetic acid
Dosages 50 mg/kg twice daily for 14 d
Administration oral
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 425.5
Formula C21H23N5O3S
CAS Number 1206161-97-8
Purity 98.32%
Solubility DMSO
Storage at -20°C
References

Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases.
Van Rompaey L, et al. J Immunol. 2013 Oct 1;191(7):3568-77. PMID: 24006460.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Filgotinib, GLPG0634 supplier, JAK, inhibitors

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