Filgotinib
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MedKoo CAT#: 206136

CAS#: 1206161-97-8 (free base)

Description: Filgotinib, also known as GLPG0634, is a potent and selective JAK1 inhibitor under investigation for the treatment of rheumatoid arthritis (RA) and Crohn's disease. It is considered a promising agent as it inhibits JAK1 selectively. Filgotinib displayed a selectivity of 30-fold for JAK1- over JAK2-dependent signaling. GLPG0634 dose-dependently inhibited Th1 and Th2 differentiation and to a lesser extent the differentiation of Th17 cells in vitro.

Chemical Structure

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Filgotinib
CAS# 1206161-97-8 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 206136
Name: Filgotinib
CAS#: 1206161-97-8 (free base)
Chemical Formula: C21H23N5O3S
Exact Mass: 425.15
Molecular Weight: 425.500
Elemental Analysis: C, 59.28; H, 5.45; N, 16.46; O, 11.28; S, 7.54

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 425 Ready to ship
200mg USD 725 Ready to ship
500mg USD 1250 Ready to ship
1g USD 2150 Ready to ship
2g USD 3850 Ready to ship
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Related CAS #: 1206101-20-3   1206161-97-8 (free base)   1540859-07-1 (HCl hydrate)   1802998-75-9 (maleate)    

Synonym: GLPG0634; GLPG 0634; GLPG-0634. Filgotinib; PubChemSID 163643231

IUPAC/Chemical Name: N-(5-(4-((1,1-dioxidothiomorpholino)methyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide.

InChi Key: RIJLVEAXPNLDTC-UHFFFAOYSA-N

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)

SMILES Code: O=C(C1CC1)NC2=NN3C(C4=CC=C(CN5CCS(CC5)(=O)=O)C=C4)=CC=CC3=N2.

Appearance: White to off-white-solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: GLPG0634 was formulated in polyethyleneglycol 200/0.9% NaCl (60/40; v/v) for i.v. administration and in 0.5% (v/v) methylcellulose for oral administration for all in vivo studies

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Biological target: 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 activity: To further explore the consequences of cytokine inhibition, the effect of GLPG0634 toward Th1 and Th2 differentiation was analyzed by measuring IFN-γ or IL-13 mRNA expression levels (Fig. 2). As expected, GLPG0634 dose-dependently inhibited the differentiation of Th2 cells mediated by IL-4, a cytokine that signals through JAK1 and JAK3. GLPG0634 also inhibited Th1 differentiation with similar potencies of 1 μM or lower. Although Th1 commitment is initiated by IL-12, a cytokine signaling through TYK2 and JAK2, the primary effect of GLPG0634 on Th1 differentiation is likely through inhibition of JAK1/JAK2-mediated signaling of IFN-γ. GLPG0634 was also tested for the ability to inhibit Th17 differentiation driven by a mixture of TGF-β, IL-23, and proinflammatory cytokines (IL-6 and IL-1β), all shown to be essential for human Th17 differentiation (18). GLPG0634 inhibited Th17 differentiation under these conditions, although with lower potency than Th1 and Th2 differentiation (Fig. 2). Reference: J Immunol. 2013 Oct 1;191(7):3568-77. https://pubmed.ncbi.nlm.nih.gov/24006460/
In vivo activity: Mouse blood and paw samples were taken with the purpose of obtaining detailed insight in the mechanism of action of GLPG0634 in vivo. Dose selection was performed in a dose range–finding experiment (data not shown), and a dose of 50 mg/kg twice daily orally was selected for the mechanistic studies. Fig. 5A shows that the 50 mg/kg dose provided full protection against inflammation as judged by analysis of the clinical score of paws. Histological analysis of the mice paws showed that GLPG0634 protected bone and cartilage from degradation (Fig. 5B). Immunohistochemistry performed on the same samples showed that GLPG0634 effectively reduced infiltration of T cells (CD3+ cells) and macrophages (F4/80+ cells) in the paw (Fig. 5C). In paws, GLPG0634 reduced the levels of inflammatory and metalloprotease genes previously linked to disease progression, explaining the beneficial role of GLPG0634 in the mouse CIA model (Fig. 5D). The mRNA levels of RANKL were also reduced in line with the decrease in the bone lesion score, suggesting that GLPG0634 might protect against bone degradation by reducing the formation and activity of osteoclasts. GLPG0634 decreased the serum levels of all cytokines and chemokines measured, including IL-6, IP-10, XCL1, and MCP-1 (Fig. 5E). These observations indicate that GLPG0634 might affect inflammatory cytokine signaling and chemoattraction of T cells and monocyte/macrophages by reducing these cytokine and chemokine levels. At the mechanistic level, the reduction of Mx1 and Mx2 mRNA levels by GLPG0634 was also observed in mouse paws (Fig. 5F), as observed in the rat (Fig. 3). Of interest, the changes in Mx1 and Mx2 gene expression in WBCs were not altered by etanercept treatment (Fig. 5G), showing that GLPG0634 specifically impacts JAK1 signaling. Reference: J Immunol. 2013 Oct 1;191(7):3568-77. https://pubmed.ncbi.nlm.nih.gov/24006460/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 41.7 97.93

Preparing Stock Solutions

The following data is based on the product molecular weight 425.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1.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. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013 Oct 1;191(7):3568-77. doi: 10.4049/jimmunol.1201348. Epub 2013 Sep 4. PMID: 24006460. 2. Lee J, Lee J, Kwok SK, Baek S, Jang SG, Hong SM, Min JW, Choi SS, Lee J, Cho ML, Park SH. JAK-1 Inhibition Suppresses Interferon-Induced BAFF Production in Human Salivary Gland: Potential Therapeutic Strategy for Primary Sjögren's Syndrome. Arthritis Rheumatol. 2018 Dec;70(12):2057-2066. doi: 10.1002/art.40589. Epub 2018 Oct 24. PMID: 29927095.
In vitro protocol: 1.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. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013 Oct 1;191(7):3568-77. doi: 10.4049/jimmunol.1201348. Epub 2013 Sep 4. PMID: 24006460. 2. Lee J, Lee J, Kwok SK, Baek S, Jang SG, Hong SM, Min JW, Choi SS, Lee J, Cho ML, Park SH. JAK-1 Inhibition Suppresses Interferon-Induced BAFF Production in Human Salivary Gland: Potential Therapeutic Strategy for Primary Sjögren's Syndrome. Arthritis Rheumatol. 2018 Dec;70(12):2057-2066. doi: 10.1002/art.40589. Epub 2018 Oct 24. PMID: 29927095.
In vivo protocol: 1.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. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol. 2013 Oct 1;191(7):3568-77. doi: 10.4049/jimmunol.1201348. Epub 2013 Sep 4. PMID: 24006460. 2. Lee J, Lee J, Kwok SK, Baek S, Jang SG, Hong SM, Min JW, Choi SS, Lee J, Cho ML, Park SH. JAK-1 Inhibition Suppresses Interferon-Induced BAFF Production in Human Salivary Gland: Potential Therapeutic Strategy for Primary Sjögren's Syndrome. Arthritis Rheumatol. 2018 Dec;70(12):2057-2066. doi: 10.1002/art.40589. Epub 2018 Oct 24. PMID: 29927095.

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1: Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021 Jul;80(7):865-875. doi: 10.1136/annrheumdis-2020-219012. Epub 2021 Mar 19. PMID: 33741556; PMCID: PMC8237188.


2: Namour F, Anderson K, Nelson C, Tasset C. Filgotinib: A Clinical Pharmacology Review. Clin Pharmacokinet. 2022 Jun;61(6):819-832. doi: 10.1007/s40262-022-01129-y. Epub 2022 May 31. PMID: 35637376; PMCID: PMC9249714.


3: Dhillon S, Keam SJ. Filgotinib: First Approval. Drugs. 2020 Dec;80(18):1987-1997. doi: 10.1007/s40265-020-01439-0. Erratum in: Drugs. 2021 Feb;81(2):297. PMID: 33237566; PMCID: PMC7858213.


4: D'Amico F, Magro F, Peyrin-Biroulet L, Danese S. Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis. J Crohns Colitis. 2022 Jun 24;16(5):835-844. doi: 10.1093/ecco-jcc/jjab206. PMID: 34791103; PMCID: PMC9228886.


5: Westhovens R. Filgotinib in rheumatoid arthritis. Expert Rev Clin Immunol. 2023 Feb;19(2):135-144. doi: 10.1080/1744666X.2023.2149495. Epub 2022 Nov 21. PMID: 36396615.


6: Kim ES, Keam SJ. Filgotinib in Rheumatoid Arthritis: A Profile of Its Use. Clin Drug Investig. 2021 Aug;41(8):741-749. doi: 10.1007/s40261-021-01055-0. Epub 2021 Jul 25. Erratum in: Clin Drug Investig. 2022 Jan;42(1):101. PMID: 34304373; PMCID: PMC8613087.


7: Feagan BG, Danese S, Loftus EV Jr, Vermeire S, Schreiber S, Ritter T, Fogel R, Mehta R, Nijhawan S, Kempiński R, Filip R, Hospodarskyy I, Seidler U, Seibold F, Beales ILP, Kim HJ, McNally J, Yun C, Zhao S, Liu X, Hsueh CH, Tasset C, Besuyen R, Watanabe M, Sandborn WJ, Rogler G, Hibi T, Peyrin-Biroulet L. Filgotinib as induction and maintenance therapy for ulcerative colitis (SELECTION): a phase 2b/3 double-blind, randomised, placebo-controlled trial. Lancet. 2021 Jun 19;397(10292):2372-2384. doi: 10.1016/S0140-6736(21)00666-8. Epub 2021 Jun 3. PMID: 34090625.


8: Genovese MC, Kalunian K, Gottenberg JE, Mozaffarian N, Bartok B, Matzkies F, Gao J, Guo Y, Tasset C, Sundy JS, de Vlam K, Walker D, Takeuchi T. Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy: The FINCH 2 Randomized Clinical Trial. JAMA. 2019 Jul 23;322(4):315-325. doi: 10.1001/jama.2019.9055. Erratum in: JAMA. 2020 Feb 4;323(5):480. PMID: 31334793; PMCID: PMC6652745.


9: Richez C, Truchetet ME. Evaluating filgotinib for the treatment of rheumatoid arthritis. Expert Opin Pharmacother. 2021 Dec;22(18):2435-2444. doi: 10.1080/14656566.2021.1967929. Epub 2021 Aug 26. PMID: 34402699.


10: Combe B, Kivitz A, Tanaka Y, van der Heijde D, Simon JA, Baraf HSB, Kumar U, Matzkies F, Bartok B, Ye L, Guo Y, Tasset C, Sundy JS, Jahreis A, Genovese MC, Mozaffarian N, Landewé RBM, Bae SC, Keystone EC, Nash P. Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. Ann Rheum Dis. 2021 Jul;80(7):848-858. doi: 10.1136/annrheumdis-2020-219214. Epub 2021 Jan 27. PMID: 33504485; PMCID: PMC8237199.


11: Westhovens R, Rigby WFC, van der Heijde D, Ching DWT, Stohl W, Kay J, Chopra A, Bartok B, Matzkies F, Yin Z, Guo Y, Tasset C, Sundy JS, Jahreis A, Mozaffarian N, Messina OD, Landewé RB, Atsumi T, Burmester GR. Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial. Ann Rheum Dis. 2021 Jun;80(6):727-738. doi: 10.1136/annrheumdis-2020-219213. Epub 2021 Jan 15. PMID: 33452004; PMCID: PMC8142453.


12: Mannucci A, D'Amico F, El Saadi A, Peyrin-Biroulet L, Danese S. Filgotinib for moderately to severely active ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2022 Oct;16(10):927-940. doi: 10.1080/17474124.2022.2138857. Epub 2022 Nov 14. PMID: 36278878.


13: Labetoulle R, Paul S, Roblin X. Filgotinib for the treatment of Crohn's disease. Expert Opin Investig Drugs. 2018 Mar;27(3):295-300. doi: 10.1080/13543784.2018.1442433. Epub 2018 Feb 28. PMID: 29448862.


14: Fanizza J, D'Amico F, Lauri G, Martinez-Dominguez SJ, Allocca M, Furfaro F, Zilli A, Fiorino G, Parigi TL, Radice S, Peyrin-Biroulet L, Danese S. The role of filgotinib in ulcerative colitis and Crohn's disease. Immunotherapy. 2023 Nov 27. doi: 10.2217/imt-2023-0116. Epub ahead of print. PMID: 38009327.


15: Taylor PC, Abdul Azeez M, Kiriakidis S. Filgotinib for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs. 2017 Oct;26(10):1181-1187. doi: 10.1080/13543784.2017.1372422. Epub 2017 Aug 29. PMID: 28838249.


16: Ho Lee Y, Gyu Song G. Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis. J Clin Pharm Ther. 2020 Aug;45(4):674-681. doi: 10.1111/jcpt.13142. Epub 2020 Jun 3. PMID: 32495356.


17: Tanaka Y, Kavanaugh A, Wicklund J, McInnes IB. Filgotinib, a novel JAK1-preferential inhibitor for the treatment of rheumatoid arthritis: An overview from clinical trials. Mod Rheumatol. 2022 Jan 5;32(1):1-11. doi: 10.1080/14397595.2021.1902617. PMID: 33740386.


18: Winthrop KL, Tanaka Y, Takeuchi T, Kivitz A, Matzkies F, Genovese MC, Jiang D, Chen K, Bartok B, Jahreis A, Besuyen R, Burmester GR, Gottenberg JE. Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years. Ann Rheum Dis. 2022 Feb;81(2):184-192. doi: 10.1136/annrheumdis-2021-221051. Epub 2021 Nov 5. PMID: 34740884; PMCID: PMC8762003.


19: Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, Caporali R, Edwards CJ, Hyrich KL, Pope JE, de Souza S, Stamm TA, Takeuchi T, Verschueren P, Winthrop KL, Balsa A, Bathon JM, Buch MH, Burmester GR, Buttgereit F, Cardiel MH, Chatzidionysiou K, Codreanu C, Cutolo M, den Broeder AA, El Aoufy K, Finckh A, Fonseca JE, Gottenberg JE, Haavardsholm EA, Iagnocco A, Lauper K, Li Z, McInnes IB, Mysler EF, Nash P, Poor G, Ristic GG, Rivellese F, Rubbert-Roth A, Schulze-Koops H, Stoilov N, Strangfeld A, van der Helm-van Mil A, van Duuren E, Vliet Vlieland TPM, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):3-18. doi: 10.1136/ard-2022-223356. Epub 2022 Nov 10. Erratum in: Ann Rheum Dis. 2023 Mar;82(3):e76. PMID: 36357155.


20: Grimm SE, Wijnen B, Riemsma R, Fayter D, Armstrong N, Ahmadu C, Brandts L, Misso K, Kirwan JR, Kleijnen J, Joore MA. Filgotinib for Moderate to Severe Rheumatoid Arthritis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics. 2021 Dec;39(12):1397-1410. doi: 10.1007/s40273-021-01080-z. Epub 2021 Aug 27. PMID: 34448148; PMCID: PMC8599377.