BMS-986202

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which can regulate the signaling of multiple pro-inflammatory cytokines, including IL12, IL23 and type I interferon (IFNα/β), and its inhibitors can treat autoimmune diseases caused by the abnormal expression of IL12 and IL23. Interest in TYK2 JH2 inhibitors has increased as a result of safety concerns with JAK inhibitors. This overview introduces TYK2 JH2 inhibitors that are already on the market, including Deucravactinib (BMS-986165), as well as those currently in clinical trials, such as BMS-986202, NDI-034858, and ESK-001.

Janus kinases (JAKs) are central components in cytokine signaling pathways. A number of small molecule JAK inhibitors have been approved to treat a wide range of inflammatory and autoimmune diseases. Due to safety concerns of pan-JAK inhibition, the thrust of current research is toward the discovery of isoform-selective JAK inhibitors. Selective inhibition of tyrosine kinase 2 (TYK2) has the potential to balance efficacy and safety. Substantial efforts have been made to develop selective TYK2 inhibitors: Deucravacitinib (BMS-986165) is a representative allosteric inhibitor that has been approved by the FDA, and ropsacitinib (PF-06826647) is an active site-directed inhibitor currently being evaluated in clinical trials. Herein, we outline the key roles of TYK2 in diseases, review the advances of selective TYK2 inhibitors, and finally discuss future perspectives and challenges in the development of TYK2 inhibitors.