deucravacitinib   Click here for help

GtoPdb Ligand ID: 10432

Synonyms: BMS-986165 | BMS986165 | compound 11 [PMID: 31318208} | Sotyktu® | Tyk2-IN-4
Approved drug Immunopharmacology Ligand
deucravacitinib is an approved drug (FDA (2022), EMA (2023))
Compound class: Synthetic organic
Comment: Deucravacitinib (BMS-986165) is a selective, orally active, allosteric inhibitor of the Janus kinase family enzyme, tyrosine kinase 2 (TYK2) [2,5]. The deuteromethyl amide group confers selectivity by virtue of binding to a pocket in the TYK2 JH2 pseudokinase domain.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 135.95
Molecular weight 422.18
XLogP 1.16
No. Lipinski's rules broken 0
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Canonical SMILES CNC(=O)c1nnc(cc1Nc1cccc(c1OC)c1ncn(n1)C)NC(=O)C1CC1
Isomeric SMILES COc1c(cccc1c1ncn(n1)C)Nc1cc(nnc1C(=O)NC([2H])([2H])[2H])NC(=O)C1CC1
InChI InChI=1S/C20H22N8O3/c1-21-20(30)16-14(9-15(25-26-16)24-19(29)11-7-8-11)23-13-6-4-5-12(17(13)31-3)18-22-10-28(2)27-18/h4-6,9-11H,7-8H2,1-3H3,(H,21,30)(H2,23,24,25,29)/i1D3
Immunopharmacology Comments
TYK2 associates with the IL-23 cytokine receptor to induce STAT-mediated regulation of genes that are involved in expansion and maintenance of TH17 and TC17 cells, and this pathway is activated in and drives pathology in psoriatic disease. TYK2-selective inhibitors are proposed to facilitate targeted disruption this cytokine-kinase-T cell axis in psoriasis [4]. Deucravacitinib (BMS-986165) achieves its selectivity by targeting the JH2 pseudokinase domain of TYK2 rather than its orthosteric ATP binding domain [5]. It was the first pseudokinase-directed therapeutic to reach clinical evaluation as an oral treatment for autoimmune diseases. It has exhibited efficacy in several murine models of autoimmune disease and is reported to block signalling and functional responses in human cells that are known to drive autoimmune pathology (e.g.Th17, Th1, B cells, and myeloid cells) [1]. It was (FDA) approved to treat plaque psoriasis in 2022.