JTE-461

JTE-461 is an orally bioavailable small molecule inhibitor of salt-inducible kinase 2 (SIK2), currently under development by Shionogi for the treatment of chronic spontaneous urticaria (CSU). SIK2 is a member of the AMPK-related kinase family that plays a critical role in immune homeostasis by regulating the production of pro-inflammatory (e.g., TNF-α, IL-12) and anti-inflammatory (e.g., IL-10) cytokines in myeloid cells. By inhibiting SIK2, JTE-461 is designed to suppress the inflammatory signaling pathways that drive mast cell degranulation and skin lesions in CSU patients. The compound was originally discovered by Japan Tobacco and licensed to Shionogi for clinical development, and it is currently being evaluated in Phase 1 clinical trials to assess its safety, pharmacokinetics, and potential drug-drug interactions.