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DEUCRAVACITINIB | DEUCRAVACITINIB : allosteric inhibitor of TYK2
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
TYK2 (Other variant:JH2 specific)
  • IC50:0.2 nM
  • Ki:0.02 nM
  • IC50:2 nM
  • IC50:9 nM
  • IC50:13 nM
Allosteric
up to 100 nM

Selectivity

In Vitro Selectivity Assessment
JAK1

Gene ID: P23458

Organism: Homo sapiens

Family: Tyr protein kinase family

Potency: IC50 - 1 nM

Potency Assay Off-Target:
Selectivity within target family: Highly specific for binding to TYK2 JH2 and does not show any sign ...
In Cell Selectivity Assessment
Selectivity Assessment Description:
low functional activity in JAK1/JAK3 dependent IL-2 stimulated cellular assay (IC50 = 592 nM); weak ...

Potency
Cellular
In Vitro

TYK2 (Other variant:JH2 specific)

Mode of Action: Allosteric

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b00444

In Vivo Validations

Mouse
Dose: 1 mg/Kg
Route of delivery: Intravenous
Plasma half life: 4.2 h
Systemic clearance: 13.2 mL/min/Kg
Volume of Distribution at Steady-State: 2.9 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b00444

Dose: 10 mg/Kg
Route of delivery: Oral
Cmax: 7.5 uM
Area Under the Curve:: 36.4 uM*h
Bioavailability: 122%

DOI Reference: 10.1021/acs.jmedchem.9b00444

Dog
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 4.6 h
Systemic clearance: 6.8 mL/min/kg
Volume of Distribution at Steady-State: 2.3 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b00444

Dose: 10 mg/Kg
Route of delivery: Oral
Cmax: 6.9 uM
Area Under the Curve:: 73.6 uM*h
Bioavailability: 128%

DOI Reference: 10.1021/acs.jmedchem.9b00444

Monkey (Cynomolgus)
Dose: 2 mg/Kg
Route of delivery: Intravenous
Plasma half life: 5.3 h
Systemic clearance: 4.8 mL/min/Kg
Volume of Distribution at Steady-State: 2 L/Kg

DOI Reference: 10.1021/acs.jmedchem.9b00444

Dose: 10 mg/Kg
Route of delivery: Oral
Cmax: 5.9 uM
Area Under the Curve:: 75.6 uM*h
Bioavailability: 87%

DOI Reference: 10.1021/acs.jmedchem.9b00444

Chemical Information

Molecular Formula C20H22N8O3
SMILEs [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ncn(C)n2)c1OC
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
Molecular weight 425.20 Da
AlogP 1.7324
HBond acceptors 11
HBond donors 3
Atoms 53

References

Publications

Cross References

canSARChEMBLBindingDB

Vendors

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Expert Reviews

by SERP
(on 9 Feb 2023 )
Cellular Use Rating
In Model Organisms
Exquisite selectivity over the other JAK family members and more broadly over the kinome. Cellular activity (IC50) is achieved below 10nM in human cells and the IC50 is 13nM in human whole blood. However,...
by SERP
(on 20 Mar 2023 )
Cellular Use Rating
In Model Organisms
Although DEUCRAVACITINIB is a highly selective and allosteric inhibitor of TYK2, a structurally related inactive control would be an additional plus. In the absence of a timely resolved PD/PD experiment,...
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