08Aug 2023
Differences in JAK Isoform Selectivity Among Different Types of JAK Inhibitors Evaluated for Rheumatic Diseases Through In Vitro Profiling

Differences in JAK Isoform Selectivity Among Different Types of JAK Inhibitors Evaluated for Rheumatic Diseases Through In Vitro Profiling

The study compared the selectivity of JAK inhibitors (Jakinibs) for different JAK isoforms and cytokines in vitro. The researchers analyzed 10 Jakinibs, finding that some were pan-Jakinibs, effectively suppressing multiple JAK family members, while others showed varying degrees of selectivity for specific JAK isoforms. In human leukocytes and peripheral blood mononuclear cells, Jakinibs predominantly inhibited JAK1-dependent cytokines like IL-2, IL-6, and interferons. Novel Jakinibs displayed high selectivity, such as ritlecitinib, which showed specific suppression of IL-2 signaling and high selectivity for JAK3. The study concluded that cellular inhibition of JAK/STAT signaling did not directly correspond to JAK kinase activity inhibition.

  • #rheumatology

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