Filgotinib

Filgotinib

Clinical data
Routes of administration	Oral
ATC code	L01XE18 (WHO)
Pharmacokinetic data
Biological half-life	6 hours
Identifiers
IUPAC 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
Synonyms	GLPG0634
CAS Number	1206161-97-8 Y
PubChem CID	49831257
IUPHAR/BPS	7913
ChemSpider	28189566 Y
UNII	3XVL385Q0M
ChEMBL	CHEMBL3301607 N
Chemical and physical data
Formula	C21H23N5O3S
Molar mass	425.50402 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(C1CC1)NC2=NN3C(C4=CC=C(CN5CCS(CC5)(=O)=O)C=C4)=CC=CC3=N2
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) Y Key:RIJLVEAXPNLDTC-UHFFFAOYSA-N Y
NY (what is this?)

Filgotinib (code name GLPG0634) is a drug which is currently under investigation for the treatment of rheumatoid arthritis (RA) and Crohn's disease. It was developed by the Belgian biotech company Galapagos NV.

Filgotinib is a Janus kinase inhibitor with selectivity for subtype JAK1 of this enzyme. It is considered a promising agent as it inhibits JAK1 selectively. Less selective JAK inhibitors (e.g. tofacitinib) are already being marketed. They show long-term efficacy in the treatment of various inflammatory diseases. However, their lack of selectivity leads to dose-limiting side effects. It is thought that inhibition of all JAK isoenzymes is beneficial in rheumatoid arthritis. However, pan-JAK inhibition might also lead to unwanted side effects that might not outweigh its benefits. This is the rationale for the development of newer and more selective inhibitors like filgotinib.

The signal transmission of large numbers of proinflammatory cytokines is dependent on JAK1. Inhibition of JAK2 may also contribute to the efficacy against RA. Nonetheless it is thought that JAK2 inhibition might lead to anemia and thrombopenia by interference with erythropoietin and thrombopoietin and granulocyte-macrophage colony-stimulating factor. Therefore, one might prefer to choose a more selective JAK1 inhibitor as a primary therapeutic option. Filgotinib exerts a 30-fold selectivity for JAK1 compared to JAK2. It is however still to be seen to what extent JAK2 inhibition should be avoided.

The efficacy of filgotinib is currently studied in a phase2b program (DARWIN trial 1, 2) with involvement of 886 rheumatoid arthritis patients and 180 Crohn's disease patients.