JAK inhibitors for rheumatoid arthritis

Introduction: JAK (Janus kinase) is a type of non-receptor tyrosine kinase that includes JAK1, JAK2, JAK3, and Tyk2. Currently, there are five JAK inhibitors approved for treating rheumatoid arthritis. These inhibitors vary in their selectivity for different JAK isoforms.

Area covered: This review outlines the mode of actions and the results of Phase III trials of the JAK inhibitors which have been approved for the treatment of rheumatoid arthritis.

Expert commentary: JAK inhibitors have the potential to finely tune immunity and inflammation in patients with rheumatoid arthritis. The in vitro data indicates that IL-6 signaling is suppressed by all JAK inhibitors, while tofacitinib exhibits the most extensive suppression of cytokines via the JAK pathway. Peficitinib suppresses common gamma cytokines, and filgotinib suppresses interferon. Furthermore, baricitinib and upadacitinib appear to be inclined towards suppressing interferon and the IL-12 family. Despite their specific target profiles, any of these drugs can inhibit other JAKs if their blood levels surpass a certain threshold. As a result, predicting in vivo selectivity remains a challenging task. JAK inhibitor seems to be a vital treatment option for difficult-to-treat rheumatoid arthritis patients, and it is expected that precision medicine approaches will enhance its effectiveness in the future.

Comments：

These drugs work by inhibiting JAK enzymes, which are involved in the signaling pathways that lead to inflammation and immune responses. By targeting these enzymes, JAK inhibitors can help reduce the symptoms of rheumatoid arthritis and slow down the progression of the disease.

The different JAK inhibitors that have been approved for the treatment of rheumatoid arthritis have varying degrees of selectivity for different JAK isoforms. For example, tofacitinib exhibits the most extensive suppression of cytokines via the JAK pathway, while peficitinib suppresses common gamma cytokines and filgotinib suppresses interferon. Baricitinib and upadacitinib appear to be inclined towards suppressing interferon and the IL-12 family. However, it is important to note that all of these drugs can inhibit other JAKs if their blood levels surpass a certain threshold, making it difficult to predict in vivo selectivity.

Despite these challenges, JAK inhibitors have proven to be effective in treating rheumatoid arthritis, particularly in patients who have not responded to other treatments. Precision medicine approaches may help improve the effectiveness of these drugs in the future by allowing for more targeted and personalized treatment plans for individual patients. Overall, JAK inhibitors represent a promising avenue for the treatment of rheumatoid arthritis and offer hope for improved outcomes for patients with this challenging disease.

Related Products

Cat.No.	Product Name	Information
S5001	Tofacitinib (CP-690550) Citrate	Tofacitinib citrate (CP-690550, Tasocitinib) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. Tofacitinib citrate has anti-infection activity.

Related Targets

Anti-infection JAK