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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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
InChI Key BZZKEPGENYLQSC-FIBGUPNXSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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 - 5
⤷ pKi 10.7 (Ki 2x10-11 M) [5]
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 - 5
⤷ pIC50 9.7 (IC50 2x10-10 M) [5]
Description: Binding to TYK2's JH2 pseudokinase domain in a biochemical binding assay.
Janus kinase 1 Hs Allosteric modulator Inhibition 9.0 pIC50 - 5
⤷ pIC50 9.0 (IC50 1x10-9 M) [5]
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 - 5
⤷ pIC50 6.7 (IC50 1.93x10-7 M) [5]