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Filgotinib [1206161-97-8]

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Referencia HY-18300-5mg

embalaje : 5mg

Marca : MedChemExpress

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Descripciòn

Filgotinib (GLPG0634) is a selective, orally available JAK1 inhibitor with anti-inflammatory and antiviral activities. Filgotinib can effectively inhibit the activities of JAK1, JAK2, JAK3 and TYK2 with IC₅₀ values of 10 nM, 28 nM, 810 nM and 116 nM, respectively. Filgotinib also inhibits HIV-1 driven gene transcription and reduces proliferation of HIV-1 infected cells. Filgotinib can be used in the study of rheumatoid arthritis and inflammatory bowel disease^[1]^[2]^[3].

IC₅₀ & Target^[1]

JAK1

10 nM (IC₅₀)

JAK2

28 nM (IC₅₀)

Tyk2

116 nM (IC₅₀)

JAK3

810 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
BaF3	IC₅₀	1.43 μM Compound: 5	Inhibition of JAK1 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay Inhibition of JAK1 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay	[PMID: 32527540]
BaF3	IC₅₀	13.26 μM Compound: 5	Inhibition of JAK3 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay Inhibition of JAK3 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay	[PMID: 32527540]
BaF3	IC₅₀	4.45 μM Compound: 5	Inhibition of JAK2 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay Inhibition of JAK2 (unknown origin) expressed in mouse BAF3 cells assessed as antiproliferative activity by cell-based assay	[PMID: 32527540]
BaF3	IC₅₀	4546 nM Compound: 65, GLPG0634	Inhibition of JAK2 in IL3-induced human BaF3 cells assessed as cell proliferation Inhibition of JAK2 in IL3-induced human BaF3 cells assessed as cell proliferation	[PMID: 25369270]
BaF3	IC₅₀	4546 nM Compound: GLPG0634	Antiproliferative activity against mouse BaF3 cells assessed as IL-3-induced inhibition of cell growth incubated for 40 hrs Antiproliferative activity against mouse BaF3 cells assessed as IL-3-induced inhibition of cell growth incubated for 40 hrs	[PMID: 24006460]
CWR22R	IC₅₀	>10000 nM Compound: 65, GLPG0634	Inhibition of JAK2 in PRL-induced human 22Rv1 cells assessed as pSTAT5 Inhibition of JAK2 in PRL-induced human 22Rv1 cells assessed as pSTAT5	[PMID: 25369270]
CWR22R	IC₅₀	>10 μM Compound: 65, GLPG0634	Inhibition of JAK2 in PRL-induced human 22Rv1 cells assessed as pSTAT5 Inhibition of JAK2 in PRL-induced human 22Rv1 cells assessed as pSTAT5	[PMID: 25369270]
HeLa	IC₅₀	1045 nM Compound: 65, GLPG0634	Inhibition of JAK1/JAK2 in OSM-induced human HeLa cells assessed as STAT1 reporter Inhibition of JAK1/JAK2 in OSM-induced human HeLa cells assessed as STAT1 reporter	[PMID: 25369270]
T-cell	IC₅₀	1.127 nM Compound: GLPG0634	Inhibition of JAK1/TYK2 in human whole blood assessed as reduction in IFN-alpha-induced STAT1 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IFN-alpha addition and measured after 20 mins by flow cytometry analysis Inhibition of JAK1/TYK2 in human whole blood assessed as reduction in IFN-alpha-induced STAT1 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IFN-alpha addition and measured after 20 mins by flow cytometry analysis	[PMID: 24006460]
T-cell	IC₅₀	17453 nM Compound: GLPG0634	Inhibition of JAK2 in human whole blood assessed as reduction in GM-CSF-induced STAT5 phosphorylation in CD3-positive T cell preincubated with compound for 30 mins followed by GM-CSF addition and measured after 20 mins by flow cytometry analysis Inhibition of JAK2 in human whole blood assessed as reduction in GM-CSF-induced STAT5 phosphorylation in CD3-positive T cell preincubated with compound for 30 mins followed by GM-CSF addition and measured after 20 mins by flow cytometry analysis	[PMID: 24006460]
T-cell	IC₅₀	1789 nM Compound: GLPG0634	Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2-induced STAT5 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IL-2 addition and measured after 20 mins by flow cytometry analysis Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2-induced STAT5 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IL-2 addition and measured after 20 mins by flow cytometry analysis	[PMID: 24006460]
T-cell	IC₅₀	629 nM Compound: GLPG0634	Inhibition of JAK1 in human whole blood assessed as reduction in IL6-induced STAT1 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IL-6 addition and measured after 20 mins by flow cytometry analysis Inhibition of JAK1 in human whole blood assessed as reduction in IL6-induced STAT1 phosphorylation in CD4+ T cells preincubated with compound for 30 mins followed by IL-6 addition and measured after 20 mins by flow cytometry analysis	[PMID: 24006460]
TF-1	IC₅₀	3524 nM Compound: 65, GLPG0634	Inhibition of JAK2 in IL3-induced human TF1 cells assessed as pSTAT5 Inhibition of JAK2 in IL3-induced human TF1 cells assessed as pSTAT5	[PMID: 25369270]
THP-1	IC₅₀	154 nM Compound: 65, GLPG0634	Inhibition of JAK1/JAK3 in IL4-induced human THP1 cells assessed as pSTAT6 Inhibition of JAK1/JAK3 in IL4-induced human THP1 cells assessed as pSTAT6	[PMID: 25369270]
THP-1	IC₅₀	3364 nM Compound: 65, GLPG0634	Inhibition of JAK1/JAK2 in IFNgamma-induced human THP1 cells assessed as pSTAT1 Inhibition of JAK1/JAK2 in IFNgamma-induced human THP1 cells assessed as pSTAT1	[PMID: 25369270]
U2OS	IC₅₀	436 nM Compound: 65, GLPG0634	Inhibition of JAK1/TYK2 in IFN-alphaB2-induced human U2OS cells assessed as pSTAT1 Inhibition of JAK1/TYK2 in IFN-alphaB2-induced human U2OS cells assessed as pSTAT1	[PMID: 25369270]

In Vitro

Filgotinib (0.1, 1 and 10 μM) inhibits the differentiation of Th2 cells and Th1 cells in a dose-dependent manner^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Filgotinib (0.1, 0.3, 1, 3, 10 and 30 mg/kg, i.g.; once daily for 15 days) produces dose-dependent bone damage protection and prevents the development of inflammation in a rat model of collagen-induced arthritis^[1].

Pharmacokinetic analysis of GLPG0634 in mice^[1]

Route	Dose (mg/kg)	C₀ or C₀ (ng/mL)	T_max (h)	T_1/2 (h)	Cl (L•h/kg)	V_ss (L/kg)	F (%)
i.v.	1	637	/	2.5	2.9	6	/
p.o.	5	920	0.5	1.7	/	/	100

Pharmacokinetic analysis of GLPG0634 in rats^[1]

Route	Dose (mg/kg)	C₀ or C₀ (ng/mL)	T_max (h)	T_1/2 (h)	Cl (L•h/kg)	V_ss (L/kg)	F (%)
i.v.	1	1407	/	1.6	1.4	1.8	/
p.o.	5	310	2.2	3.9	/	/	45

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	therapeutic rat CIA model^[1]
Dosage:	0.1, 0.3, 1, 3, 10 and 30 mg/kg
Administration:	i.g. 1 time per day for 15 days
Result:	Reduced inflammatory cell infiltration while protecting articular cartilage and bone at a dose of 1 mg/kg. Reduced serum levels of inflammatory cytokines and chemokines including IL-6, IP-10, XCL1, and MCP-1.

Ensayo clínico

Peso molecular

425.50

Fòrmula

C₂₁H₂₃N₅O₃S

No. CAS

1206161-97-8

Appearance

Solid

Color

Off-white to gray

SMILES

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

Envío

Room temperature in continental US; may vary elsewhere.

Almacenamiento

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvente y solubilidad

In Vitro:

DMSO : 25 mg/mL (58.75 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.3502 mL	11.7509 mL	23.5018 mL
5 mM	0.4700 mL	2.3502 mL	4.7004 mL
10 mM	0.2350 mL	1.1751 mL	2.3502 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Protocol 4

Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution
Protocol 5

Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.88 mM); Clear solution

Pureza y Documentación

Purity: 99.77%

Ficha de datos (282 KB) SDS (393 KB)

COA (252 KB) RP-HPLC (258 KB) MS (70 KB)

Instrucciones de manejo (2659 KB)

Referencias

[1]. Van Rompaey L, et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013, 191(7), 3568-3577. [Content Brief]

[2]. Menet CJ, et al. Triazolopyridines as Selective JAK1 Inhibitors: From Hit Identification to GLPG0634. J Med Chem. 2014 Nov 17. [Content Brief]

[3]. Yeh, et al. "Filgotinib suppresses HIV-1–driven gene transcription by inhibiting HIV-1 splicing and T cell activation." The Journal of Clinical Investigation 130.9 (2020): 4969-4984. [Content Brief]

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Filgotinib [1206161-97-8]

Referencia HY-18300-5mg

Marca : MedChemExpress

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