Ritlecitinib (PF-06651600) is a highly selective, orally active, irreversible covalent JAK3 inhibitor (IC50 = 33 nM) with no significant activity against JAK1, JAK2, or TYK2 (IC50 >10 µM). It blocks signaling mediated by γ-chain cytokines such as IL-2 and IL-15 by inhibiting downstream STAT phosphorylation. Ritlecitinib suppresses Th1 and Th17 cell differentiation and demonstrates efficacy in preclinical models of autoimmune diseases including alopecia areata, adjuvant-induced arthritis, and experimental autoimmune encephalomyelitis.
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