For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>GLPG0634(filgotinib) is a selective JAK1 inhibitor with IC50 of 10 nM, 28 nM, 810 nM, and 116 nM for JAK1, JAK2, JAK3, and TYK2, respectively.<br><br>IC50 value: 10/28/810/116 nM(JAK1/JAK2/JAK3/Tyk2)<br><br>Target: JAK;Tyk2<br><br>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 [1].<br><br>in vivo: Following oral administration, the absolute bioavailability was moderate in rats (45%) and high in mice (～100%). GLPG0634 (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 [1].</p>
| Catalog Number | I000761 |
| CAS Number | 1206161-97-8 |
| Synonyms | N-[5-[4-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]phenyl]-[1,2,4]triazolo[1,5-a]pyridin-2-yl]cyclopropanecarboxamide |
| Molecular Formula | C₂₁H₂₃N₅O₃S |
| Purity | ≥95% |
| Target | JAK |
| Solubility | DMSO: ≥ 34 mg/mL |
| Storage | Store at -20C |
| IC50 | 10/28/810/116 nM(JAK1/JAK2/JAK3/Tyk2) |
| InChI | 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) |
| InChIKey | RIJLVEAXPNLDTC-UHFFFAOYSA-N |
| SMILES | C1CC1C(=O)NC2=NN3C(=N2)C=CC=C3C4=CC=C(C=C4)CN5CCS(=O)(=O)CC5 |
| Reference | </br>1:Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Westhovens R, Taylor PC, Alten R, Pavlova D, Enríquez-Sosa F, Mazur M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P.Ann Rheum Dis. 2017 Jun;76(6):998-1008. doi: 10.1136/annrheumdis-2016-210104. Epub 2016 Dec 19. PMID: 27993829 Free Article</br>2:Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Kavanaugh A, Kremer J, Ponce L, Cseuz R, Reshetko OV, Stanislavchuk M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P.Ann Rheum Dis. 2017 Jun;76(6):1009-1019. doi: 10.1136/annrheumdis-2016-210105. Epub 2016 Dec 19. PMID: 27993828 Free Article</br>3:Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions. Namour F, Desrivot J, Van der Aa A, Harrison P, Tasset C, van/’t Klooster G.Drug Metab Lett. 2016;10(1):38-48. PMID: 26693854 </br>4:Author/’s Reply to Srinivas: /Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection/. Namour F.Clin Pharmacokinet. 2015 Dec;54(12):1297-8. doi: 10.1007/s40262-015-0336-5. No abstract available. PMID: 26482170 Free PMC Article</br>5:Comment on: /Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modelling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection/. Srinivas NR.Clin Pharmacokinet. 2015 Dec;54(12):1293-5. doi: 10.1007/s40262-015-0335-6. No abstract available. PMID: 26482169 </br>6:Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection. Namour F, Diderichsen PM, Cox E, Vayssière B, Van der Aa A, Tasset C, Van/’t Klooster G.Clin Pharmacokinet. 2015 Aug;54(8):859-74. doi: 10.1007/s40262-015-0240-z. PMID: 25681059 Free PMC Article</br>7:Triazolopyridines as selective JAK1 inhibitors: from hit identification to GLPG0634. Menet CJ, Fletcher SR, Van Lommen G, Geney R, Blanc J, Smits K, Jouannigot N, Deprez P, van der Aar EM, Clement-Lacroix P, Lepescheux L, Galien R, Vayssiere B, Nelles L, Christophe T, Brys R, Uhring M, Ciesielski F, Van Rompaey L.J Med Chem. 2014 Nov 26;57(22):9323-42. doi: 10.1021/jm501262q. Epub 2014 Nov 17. PMID: 25369270 </br>8:Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. Van Rompaey L, Galien R, van der Aar EM, Clement-Lacroix P, Nelles L, Smets B, Lepescheux L, Christophe T, Conrath K, Vandeghinste N, Vayssiere B, De Vos S, Fletcher S, Brys R, van /’t Klooster G, Feyen JH, Menet C.J Immunol. 2013 Oct 1;191(7):3568-77. doi: 10.4049/jimmunol.1201348. Epub 2013 Sep 4. PMID: 24006460 Free Article |
