deucravacitinib   Click here for help

GtoPdb Ligand ID: 10432

Synonyms: BMS-986165 | BMS986165 | compound 11 [PMID: 31318208} | Tyk2-IN-4
Immunopharmacology Ligand
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) [2,4]. The deuteromethyl amide group confers selectivity by virtue of binding to a pocket in the TYK2 JH2 pseudokinase domain.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
SMILES / InChI / InChIKey
Click here for help
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
InChI Key BZZKEPGENYLQSC-FIBGUPNXSA-N
Bioactivity Comments
BMS-986165 exhibits excellent JAK isoform and kinome selectivity. It does not bind to JAKs1-3 or to the TYK2 JH1 (ATP) binding domain, but binds avidly to TYK2's JH2 (pseudokinase) domain [3]. BMS-986165 inhibits IFNα production with an IC50 of 5 nM in vitro.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
tyrosine kinase 2 Primary target of this compound Hs Allosteric modulator Inhibition 10.7 pKi - 4
pKi 10.7 (Ki 2x10-11 M) [4]
Description: Determined in a Morrison titration by varying the concentration of the fluorescent probe in the TYK2 JH2 assay.
tyrosine kinase 2 Primary target of this compound Hs Allosteric modulator Inhibition 9.7 pIC50 - 4
pIC50 9.7 (IC50 2x10-10 M) [4]
Description: Binding to TYK2's JH2 pseudokinase domain in a biochemical binding assay.
Janus kinase 1 Hs Allosteric modulator Inhibition 9.0 pIC50 - 4
pIC50 9.0 (IC50 1x10-9 M) [4]
Description: Binding to JAK1 JH2 pseudokinase domain.
Selectivity at catalytic receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
bone morphogenetic protein receptor type 2 Hs Inhibitor Inhibition 6.7 pIC50 - 4
pIC50 6.7 (IC50 1.93x10-7 M) [4]