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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
GLPG0634 analogue, an analog of Filgotinib (GLPG0634), is a novel, potent and selective Janus kinase-JAK1 inhibitor with potential anti-inflammatory activity. It inhibits JAK1, JAK2, JAK3, and TYK2 with IC50s of 10, 28, 810, and 116 nM, respectively. It has the potential to be used for treating RA-rheumatoid arthritis. It dose-dependently reduces inflammation, cartilage, and bone degradation in the CIA model in rats and mice.
| Targets |
JAK1 (IC50 <100 nM); JAK2 (IC50 <100 nM); JAK3 (IC50 <100 nM); Tyk2 (IC50 <100 nM)
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| ln Vitro |
JAK-STAT and OSM/IL-lβ pathways are both inhibited by GLPG0634 analog (Compoun 176), with respective EC50 values ranging from 101 to 500 nM[1]. In both rats and humans, the GLPG0634 analog has microsomal stability of 76%–100%[1].
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| ln Vivo |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Filgotinib is rapidly absorbed after oral administration. Median peak plasma concentrations occurred 2-3 hours post-dose for filgotinib and 5 hours post-dose for GS-829845. Steady-state concentrations can be observed in 2-3 days for filgotinib and in 4 days for GS-829845. Food does not appear to have a significant effect on the absorption of filgotinib; therefore, the medication can be administered without regard to food. After repeated oral dosing of filgotinib 200 mg, the reported Cmax and AUCτ values of filgotinib were 2.15 ug/mL and 6.77 ugxh/mL, respectively. For GS-829845 (the major metabolite) the reported Cmax was 4.43 ug/mL and the reported AUCτ was 83.2 ugxh/mL. Of the total administered dose of filgotinib, approximately 87% undergoes renal elimination while 15% undergoes faecal elimination. Metabolism / Metabolites Carboxylesterase enzymes are involved in the metabolism of filgotinib. The carboxylesterase 2 (CES2) isoform is chiefly responsible for metabolizing filgotinib to its major metabolite, GS-829845. Although carboxylesterase 1 (CES1) plays a less prominent role in the biotransformation of filgotinib, in vitro studies have demonstrated that CES1 will partially compensate in the event of CES2 saturation. GS-829845 is thus far the only major circulating metabolite to have been identified. Biological Half-Life The half-life of filgotinib is estimated to be 7 hours, while the half-life of its active metabolite GS-829845 is estimated to be 19 hours. |
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Filgotinib is not approved in the United States by the Food and Drug Administration. No information is available on the clinical use of filgotinib during breastfeeding. The European manufacturer recommends that breastfeeding be discontinued during filgotinib therapy. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Approximately 55-59% of filgotinib is protein-bound, while 39-44% of the active metabolite GS-829845 is protein-bound. |
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| References | |||
| Additional Infomation |
Pharmacodynamics
In addition to targeted Janus kinase (JAK) 1 inhibition, filgotinib targets pro-inflammatory cytokine signalling by inhibiting IL-6 induced STAT1 phosphorylation. Serum C-reactive protein levels are also reduced in response to filgotinib administration. |
| Molecular Formula |
C23H18N6O2
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| Molecular Weight |
410.43
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| Exact Mass |
410.149
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| Elemental Analysis |
C, 67.31; H, 4.42; N, 20.48; O, 7.80
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| CAS # |
1206101-20-3
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| Related CAS # |
Filgotinib;1206161-97-8
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| PubChem CID |
49831257
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.733
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| LogP |
2.26
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
715
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RIJLVEAXPNLDTC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H23N5O3S/c27-20(17-8-9-17)23-21-22-19-3-1-2-18(26(19)24-21)16-6-4-15(5-7-16)14-25-10-12-30(28,29)13-11-25/h1-7,17H,8-14H2,(H,23,24,27)
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| Chemical Name |
N-[5-[4-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4365 mL | 12.1823 mL | 24.3647 mL | |
| 5 mM | 0.4873 mL | 2.4365 mL | 4.8729 mL | |
| 10 mM | 0.2436 mL | 1.2182 mL | 2.4365 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05323591 | Recruiting | Drug: Filgotinib | Rheumatoid Arthritis | Galapagos NV | May 3, 2022 | |
| NCT03926195 | Completed Has Results |
Drug: Filgotinib Drug: Placebo |
Rheumatoid Arthritis Psoriatic Arthritis |
Galapagos NV | May 28, 2019 | Phase 2 |
| NCT06285539 | Not yet recruiting | Drug: Filgotinib | Behcet's Disease Idiopathic Inflammatory Myopathies |
UMC Utrecht | March 2024 | Phase 2 |
| NCT05697159 | Recruiting | Drug: Larotrectinib Sulfate Procedure: Bone Scan |
Rheumatoid Arthritis Sickness Behavior |
NHS Greater Glasgow and Clyde | August 22, 2023 |
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. |
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