Discovery and Development of Deucravacitinib (BMS-986165), a Small Molecule TYK2 Inhibitor for the Treatment of Autoimmune Diseases

This chapter will describe the discovery and development of deucravacitinib (BMS-986165), a TYK2 inhibitor intended to treat multiple autoimmune disorders. The drug discovery efforts to inhibit this challenging kinase target feature phenotypic high-throughput screening to identify hits having a novel mechanism of action, structure-guided design and optimization, and a deuteration strategy to obviate a metabolic liability. The development of the commercial process to deucravacitinib is discussed, with a focus on sustainability, as well as addressing unique considerations pertaining to the deuterated portion of this API.