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FILGOTINIB: Tyrosine-protein kinase JAK1 inhibitor, treatment of rheumatoid arthritis, treatment of crohn’s disease
Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, is associated with pain, progressive disability, systemic comorbidities and early death. Filgotinib (GLPG-0634), a new selective tyrosine-protein kinase (JAK1) inhibitor, is currently in phase II clinical trials for the treatment of RA and Crohn’s disease. In in vitro biochemical and cellular and human whole blood assays, filgotinib showed selective potency, inhibiting JAK1 in the nanomolar range. In models of RA and Crohn’s disease in vivo in rodents it showed antiinflammatory efficacy. In a proof-of-concept trial in 36 RA patients with insufficient response to methotrexate, at doses of 100 mg b.i.d. and 200 mg once daily 91.7% and 75% of patients reached ACR20 scores, respectively. The pooled values for ACR20, DAS28 and C-reactive protein (CRP) change versus placebo at week 4 reached statistical significance. Of note, typical side effects of non-selective JAK inhibitors, i.e., anemia and increases in LDL cholesterol, liver enzymes and creatinine, were not detected.
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Reference£º
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem