
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.
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