JAK inhibitors: Ten years after

Area of Science:

• Immunology
• Pharmacology
• Biochemistry

Background:

• The discovery of cytokines and growth factors 50 years ago launched a new era in immunology.
• Understanding cytokine signaling led to the identification of Janus kinases (JAKs).
• Targeting JAKs emerged as a therapeutic strategy for immune and inflammatory diseases.

Purpose of the Study:

• To review the development and clinical success of JAK inhibitors (jakinibs).
• To discuss newer, selective jakinibs and those targeting multiple kinases.
• To explore the rationale for using jakinibs in treating the COVID-19 cytokine storm.

Main Methods:

• Review of scientific literature on cytokine discovery and JAK signaling.
• Analysis of the development pathway of first-generation and newer jakinibs.
• Examination of clinical data and therapeutic applications of jakinibs.

Main Results:

• Nine jakinibs are approved for rheumatologic, dermatologic, gastrointestinal, neoplastic, and COVID-19 indications.
• Jakinibs have demonstrated significant clinical success in various immune-mediated diseases.
• The application of jakinibs in managing the COVID-19 cytokine storm is supported by their mechanism of action.

Conclusions:

• Jakinibs represent a major therapeutic advance in treating immune and inflammatory diseases.
• Gaps remain in understanding the full biological activities and clinical applications of jakinibs.
• Challenges in clinical application necessitate further research and development.