Description In vitro In vivo
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Filgotinib

Description In vitro In vivo
Product Name
Filgotinib
CAS No.
1206161-97-8
Chemical Name
Filgotinib
Synonyms
GLPG0634;SYN1158;GLPG634;CS-1083;GPLG0634;Feigotini;filgotinib;GLPG0634 >=95%;GLPG0634 (analog);GLPG0634;GLPG 0634
CBNumber
CB52621138
Molecular Formula
C21H23N5O3S
Formula Weight
425.5
MOL File
1206161-97-8.mol
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Filgotinib Property

Melting point:
229 - 231°C
Density 
1.51±0.1 g/cm3(Predicted)
storage temp. 
-20°C
solubility 
Soluble in DMSO (15 mg/ml with warming)
form 
solid
pka
8.04±0.20(Predicted)
color 
Off-white
Stability:
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
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Safety

HS Code 
2921309990
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Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Warning
Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

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N-Bromosuccinimide Price

Cayman Chemical
Product number
17669
Product name
Filgotinib
Purity
≥98%
Packaging
5mg
Price
$56
Updated
2024/03/01
Cayman Chemical
Product number
17669
Product name
Filgotinib
Purity
≥98%
Packaging
1mg
Price
$25
Updated
2021/12/16
Cayman Chemical
Product number
17669
Product name
Filgotinib
Purity
≥98%
Packaging
10mg
Price
$99
Updated
2024/03/01
Cayman Chemical
Product number
17669
Product name
Filgotinib
Purity
≥98%
Packaging
25mg
Price
$166
Updated
2024/03/01
TRC
Product number
G411100
Product name
GLPG-0634(Filgotinib)
Packaging
25mg
Price
$200
Updated
2021/12/16
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Filgotinib Chemical Properties,Usage,Production

Description

Filgotinib (GLPG0634) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.

In vitro

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.

In vivo

Following 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.

Description

Filgotinib is a JAK1 inhibitor (IC50 = 10 nM). It is selective for JAK1 over JAK3 (IC50 = 810 nM) but also inhibits JAK2 and tyrosine kinase 2 (Tyk2; IC50s = 28 and 116 nM, respectively), as well as Abl, FLT1, -3, and -4, FMS, Mer, and TBK1 activity by greater than 35% in a panel of 177 tyrosine kinases at 1 μM. Filgotinib inhibits IL-6-induced phosphorylation of STAT1 in CD4+ T cells with an IC50 value of 629 nM in isolated human whole blood. It reduces hind paw macrophage and T cell infiltration and bone erosion in a rat model of collagen-induced arthritis when administered at doses ranging from 0.1 to 30 mg/kg per day for 15 days.

Characteristics

Class: non-receptor tyrosine kinase
Treatment: ulcerative colitis, rheumatoid arthritis
Elimination half-life = 6–11 h
Protein binding = 32%

Uses

GLPG-0634 (Filgotinib) is a potent, selective JAK1 inhibitor. Used as an anti-inflammatory agent, it reduces levels of inflammatory cytokines in the bones and tissue of mammals.

Mechanism of action

Filgotinib acts on the JAK-STAT pathway by selectively inhibiting JAK1 phosphorylation and preventing STAT activation, which ultimately results in reduced proinflammatory cytokine signaling.

Side effects

  • feeling sick (nausea)
  • upper respiratory tract infection
  • urinary tract infection.
  • dizziness.

Synthesis

The synthesis of Filgotinib is as follows:
With cyclopropanyl chloride in an amidated reaction in a system consisting of N-methylmorpholine and 1,4-dioxane,The amidation reaction time was 4 h,The amidation reaction temperature was 50 ° C,The molar ratio of the intermediate (III), cyclopropanyl chloride, N-methylmorpholine and 1,4-dioxane was 1: 2.8: 2.5:TLC plate to determine the reaction is completed, cooled to room temperature,Adding methylene chloride and water, separating the organic phase with water,Then washed with brine, dried over magnesium sulfate,Evaporated to dryness and the residue was purified over a silica gel column [elution solvent: ethyl acetate / n-hexane (3: 7 v / v)To obtain a solid yellowish solid,That is, Filgotinib, yield 91.2%.

Metabolism

Filgotinib has favorable metabolic stability in vitro (65%, 45%, and 87% of compound remaining in rat, dog, and human liver microsomes, respectively, after 60 min incubation; and a half-life of more than 200 min in hepatocytes for all species). Filgotinib is a substrate of P-gp, as revealed by an efflux ratio of 16 from the Caco-2 assay. In spite of the high efflux ratio, it still showed 45% and 67% oral bioavailability in rats and dogs, respectively, presumably due to its good solubility (0.18 mg/mL in water), high membrane permeability, and good metabolic stability. It exhibited low plasma protein bindings across species (48% in rats, 29% in dogs, and 32% in humans). The elimination half-lives of filgotinib were 6 and 11 hours in the Japanese and Caucasian volunteers, respectively. In both trials, the active metabolite 3 showed plasma concentrations far beyond those of filgotinib, with half-life values ranging from 17 to 20 hours, which supports once-a-day oral administration. The active metabolite 3 was formed by hydrolysis of the amide functionality to release the free amine. This metabolite is less potent than filgotinib but still maintains good JAK1 selectivity. This metabolite is believed to contribute to the overall therapeutic effects along with the parent drug.

References

Menet et al. (2014), Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634; Med. Chem., 57 9323 Rompaey et al. (2013), Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases; Immunol., 191 3568 Kavanaugh et al. (2017), Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomized dose-finding study (DARWIN 2); Rheum. Dis., 76 1009 Wang et al. ?(2019), Oncostatin M inhibits differentiation of rat stem Leydig cells in vivo and in vitro; J. Cell. Mol. Med., 23 426

Filgotinib Preparation Products And Raw materials

Raw materials

Preparation Products

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Filgotinib Suppliers

Shandong Juntai Pharmaceutical Co., LTD.
Tel
15853135817
Fax
0531-66958526
Email
sales@h2opharm.com
Country
China
ProdList
162
Advantage
55
Wuhan HSN Pharmaresearch CO., LTD.
Tel
027-63499089 18086100502
Fax
027-86589137
Email
linwell@126.com
Country
China
ProdList
211
Advantage
50
Nanjing Vcare PharmaTech Co., Ltd
Tel
025-58741518 13327700685
Email
sales@vcarepharmatech.com
Country
China
ProdList
508
Advantage
58
Shenzhen Yaoyuan R&D Center Co., Ltd
Tel
13421666688 13421666688
Email
664261110@qq.com
Country
China
ProdList
410
Advantage
58
RD International Technology Co., Limited
Tel
18024082417
Email
market@ubiochem.com
Country
China
ProdList
9266
Advantage
58
Suzhou Haijing Pharmaceutical Technology Co., Ltd
Tel
18662190408 18662190408
Email
275443226@qq.com
Country
China
ProdList
53
Advantage
58
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2922
Advantage
55
ZHIWE CHEMTECH CO LTD
Tel
021-20221225 13917446399
Fax
QQ:115820162
Email
sales@zhiwe.net
Country
China
ProdList
627
Advantage
61
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
Anhui Lianchuang Biological Medicine Co.,Ltd
Tel
0551-68779238 18056025720
Email
sales3@lcywhx.com
Country
China
ProdList
159
Advantage
57
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View Lastest Price from Filgotinib manufacturers

Hebei Zhuanglai Chemical Trading Co Ltd
Product
Filgotinib 1206161-97-8
Price
US $50.00/kg
Min. Order
1kg
Purity
99
Supply Ability
5000
Release date
2024-11-14
shandong perfect biotechnology co.ltd
Product
GLPG0634 1206161-97-8
Price
US $0.00/g
Min. Order
1g
Purity
98% HPLC
Supply Ability
1kg
Release date
2023-08-01
Hebei Mingeng Biotechnology Co., Ltd
Product
GLPG0634 ,Filgotinib 1206161-97-8
Price
US $150.00/ASSAYS
Min. Order
10g
Purity
more than 99.6%
Supply Ability
500kg/month
Release date
2021-12-03

1206161-97-8, FilgotinibRelated Search:


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  • CyclopropanecarboxaMide, N-[5-[4-[(1,1-dioxido-4-thioMorpholinyl)Methyl]phenyl][1,2,4]triazolo[1,5-a]pyridin-2-yl]-
  • GLPG0634 (analog)
  • N-[5-[4-[(1,1-Dioxido-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide
  • N-(5-(4-((1,1-Dioxidothiomorpholino)methyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide
  • Filgotinib (GLPG0634)
  • N-[5-[4-[(1,1-Dioxido-4-thiomorpholinyl)methyl]phenyl][1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide Filgotinib (GLPG0634)
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  • 1206161-97-8