Deucravacitinib (BMS-986165) is a highly potent and selective allosteric inhibitor of Tyk2 with a Ki value of 0.02 nM for binding to the Tyk2 pseudokinase domain. It is highly selective against a panel of 265 kinases and pseudokinases.
Deucravacitinib (BMS-986165) Deucravacitinib (BMS-986165) is a highly potent and selective allosteric inhibitor of Tyk2 with a Ki value of 0.02 nM for binding to the Tyk2 pseudokinase domain. It is highly selective against a panel of 265 kinases and pseudokinases.
Targets
Tyk2 (Cell-free assay) 0.02 nM
In vitro
BMS-986165 is highly differentiated from all other reported JAK/TYK2 inhibitors due to its ability to achieve an unprecedented level of selectivity for TYK2, especially over JAK1, JAK2, and JAK3.
In vivo
BMS-986165 has been identified as a highly potent and selective allosteric TYK2 inhibitor having excellent PK properties across species with minimal profiling liabilities and is orally efficacious with dose-dependent activity in a murine disease model of psoriasis. Significant activity has also been observed with 11 in other murine autoimmune disease models of colitis and lupus.
1.Schlapbach C, Conrad C. (2022) TYK-ing all the boxes in psoriasis.. J Allergy Clin Immunol, 149 (6):(1936-1939). [PMID:35341877]
2.Papp K, Gordon K, Thaçi D, Morita A, Gooderham M, Foley P, Girgis IG, Kundu S, Banerjee S. (2018) Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis.. N Engl J Med, 379 (14):(1313-1321). [PMID:30205746]
3.Wrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J, Tokarski JS, Strnad J, Zupa-Fernandez A, Cheng L et al.. (2019) Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165.. J Med Chem, 62 (20):(8973-8995). [PMID:31318208]
4.Burke JR, Cheng L, Gillooly KM, Strnad J, Zupa-Fernandez A, Catlett IM, Zhang Y, Heimrich EM, McIntyre KW, Cunningham MD et al.. (2019) Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain.. Sci Transl Med, 11 (502):(589-97). [PMID:31341059]
5.Chang Y, Xu S, Ding K. (2019) Tyrosine Kinase 2 (TYK2) Allosteric Inhibitors To Treat Autoimmune Diseases.. J Med Chem, 62 (20):(8951-8952). [PMID:31603320]
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