Ritlecitinib is potent (IC50 = 33 nM) covalent JAK3 inhibitor with exquisite selectivity over other members in its kinase class (JAK1, JAK2, TYK2).1,2 It also displays excellent kinome selectivity against 305 kinases tested. Ritlecitinib inhibits Th1 and Th17 cell differentiation and function and ameliorates symptoms in rat arthritis and mouse autoimmune encephalomyelitis models.2 It selectively targets gammac cytokine pathways while preserving JAK1-dependent anti-inflammatory signaling. Ritlecitinib also displays activity against some TEC family kinases (BTK, BMX, ITK, RLK,TEC) leading to inhibition of the cytolytic function of CD8+ T cells and NK cells.3 Low dose Ritlecitinib significantly improved T-cell responses and decreased tumor load in louse cancer models.4 It significantly prolonged allograft survival in a mouse cardiac transplantation model.
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