Deucravacitinib

Deucravacitinib (trade name Sotykto) is a first-in-class tyrosine kinase 2 (TYK2) inhibitor recently approved for the treatment of moderate to severe plaque psoriasis. Psoriasis is a chronic inflammatory skin disease characterized by the formation of red patches and scaling on the skin. Discovered by Bristol Myers Squibb (BMS), deuterated colestitinib, also known as BMS-986165, is the first JAK inhibitor containing deuterium and the first approved selective TYK2 inhibitor, showing more than 50,000-fold selectivity over JAK1, JAK2 and JAK3.
Deucravacitinib, a highly selective allosteric TYK2 inhibitor, received its first approval from the FDA in 2022 for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy protein and lipid kinases and pseudokinases with the exception of BMPR2 (IC50 = 193 nM) and JAK1 JH2 pseudokinase domain (IC50 = 1 nM). Despite its potent affinity for JAK1 JH2, deucravacitinib elicited low functional activity in a JAK1/JAK3-dependent IL-2 stimulated cellular assay. BMS-986202 displays >10,000-fold selectivity for TYK2 JH2 over a diverse panel of 273 kinases and pseudokinases that include JAK family members. Like deucravacitinib, its high binding affinity to JAK1 JH2 (IC50 = 7.8 nM) did not translate to functional activity in the cellular assay.