Tofacitinib, baricitinib and upadacitinib are the first 3 JAK inhibitors to become commercially available in the field and are the core focus of this review.

Proinflammatory cytokine activation of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway is a critical event in the pathogenesis and progression of rheumatoid arthritis.

The crucial role played by the activation of the JAK/STAT pathway in RA was further confirmed after the United States Food and Drug Administration (FDA) approval of the selective small molecule inhibitor (SMI) of JAK3, tofacitinib, for medical therapy in RA.

Aug 19, 2022 · Here, we developed a newly irreversible covalent JAK3-selective inhibitor Z583 with an IC 50 value of 0.1 nM [Michaelis constant (K m) ATP] or 10.84 nM (1 mM ATP), which exhibits excellent anti-RA effect by suppressing the activation of the JAK-STAT pathway by binding to the cysteine residue at position 909 (Cys 909) in the JAK3 subtype. We ...

Jan 5, 2022 · JAK inhibitors suppress intracellular signalling mediated by multiple cytokines involved in the pathological processes of rheumatoid arthritis and many other immune and inflammatory diseases,...

Jan 12, 2024 · Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA).

Mar 27, 2018 · In 2012, the U.S. FDA has approved Tofacitinib as an oral JAK3 inhibitor to treat adults with moderately to severely active RA. Tofacitinib is a first-in-class JAK3 inhibitor with low...

Aug 19, 2022 · Here, a highly JAK3-selective inhibitor Z583 is developed, which showed a potent inhibition of JAK3 with an IC 50 of 0.1 nM and exhibited a 4500-fold selectivity for JAK3 than other JAK subtypes.

It is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate. It can be used either as monotherapy or combination therapy with methotrexate, or other DMARDs.

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and …