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JAK inhibitors: Is specificity at all relevant?
1Translational Immunology Section, Office of Science and Technology, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
Seminars in Arthritis and Rheumatism
|November 25, 2023
Summary
Janus kinase inhibitors (JAKinibs) are evolving through three generations, with newer allosteric inhibitors showing improved safety. Further research is needed to optimize JAKinib use for immune-related diseases.
Area of Science:
- Immunology
- Pharmacology
Background:
- Cytokines are crucial for immune homeostasis, but their dysregulation causes immune-related diseases.
- Targeting cytokines or their receptors is a therapeutic strategy for inflammatory conditions.
Purpose of the Study:
- To review the development and characteristics of Janus kinase inhibitors (JAKinibs).
- To discuss the evolution of JAKinibs through three generations, focusing on selectivity and safety profiles.
Main Methods:
- Review of scientific literature on JAK inhibitors and their mechanisms of action.
- Analysis of the progression from first-generation to third-generation JAKinibs.
Main Results:
- JAKinibs target Janus kinases (JAKs) involved in cytokine receptor signaling.
- Three generations of JAKinibs exist: orthosteric multi-JAK inhibitors, selective orthosteric inhibitors, and allosteric inhibitors.
- Third-generation JAKinibs, which are allosteric, demonstrate a better safety profile.
- Development of tissue-specific JAKinibs (topical, inhaled, non-absorbable) is underway.
Conclusions:
- Understanding of JAKinib selectivity, activity, and safety is still developing.
- Further research is essential for optimizing the clinical application of JAKinibs.
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