gsk4347859

GSK4347859 is an orally bioavailable small molecule prodrug developed by GSK for the treatment of autoimmune and inflammatory diseases, primarily systemic lupus erythematosus (SLE). Upon administration, it is converted in vivo to its active form, **GSK3996401**, which acts as a potent and highly selective allosteric inhibitor of **tyrosine kinase 2 (Tyk2)**. By binding to the regulatory pseudokinase (JH2) domain of Tyk2 rather than the conserved catalytic (JH1) domain, the drug achieves high selectivity over other Janus kinases (JAK1, JAK2, and JAK3). This allosteric inhibition effectively blocks the signaling of pro-inflammatory cytokines, including interleukin-12 (IL-12), interleukin-23 (IL-23), and Type I interferons (IFN), which are key drivers in the pathogenesis of SLE. As of 2024, GSK4347859 is in early-stage clinical development, with Phase 1 studies evaluating its safety, pharmacokinetics, and pharmacodynamics in healthy volunteers and patients.

Other names

GSK3996401GSK-3996401GSK 3996401GSK-4347859GSK4347859GSK 4347859