Baricitinib

Protein target name:

JAK1, JAK2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 100 nM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:6190 HGNC:6192

Entrez gene ID:

3716 3717

UNIPROT ID:

P23458 O60674

Target alias:

Janus kinase 1, JAK1AB, JTK3, JAK1, Janus kinase 2, JTK10, THCYT3

Probe Details

Chemical Probes Portal ID:

CPP1233

Probe alias:

LY3009104, INCB028050, 3JW

PubChem CID:

44205240

ChEMBL ID:

CHEMBL2105759

SMILES string:

N#CCC1(N2N=CC(C3=C4C(NC=C4)=NC=N3)=C2)CN(S(=O)(CC)=O)C1

InChi Key:

XUZMWHLSFXCVMG-UHFFFAOYSA-N

Control compound:

INCB027753,INCB029843

Orthogonal probe:

RuxolitinibFilgotinib

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

5.9 nM JAK1, 5.7 nM JAK2

Potency assay:

Biochemical Assay (TR-FRET)

PDB ID for probe-target interaction (3D structure):

4W9X

Structure-activity relationship:

yes

Off target activity

Potency (off target):

IC50

Off target protein and potency:

Tyk2 53 nM, JAK3 560 nM, AAK1 17.2 nM, BIKE 39.8 nM, GAK134.4 nM, MPSK1 68.5 nM

Potency assay (off target):

TR-FRET, ITC

Probe Selectivity in Vitro:

JAK3 IC50 ~ 560 nM, ~10-fold selectivity against Tyk2 (IC50 = 53 nM), c-Met (IC50 > 10,000 nM) and Chk2 (IC50 > 1,000 nM). Tested @ 500 nM against a diverse panel of 28 kinases with no significant inhibition observed. Additional Off Targets are (Kd): AAK1 17.2 nM, BIKE 39.8 nM, GAK134.4 nM , MPSK1 68.5 nM

In cell validation

On target activity in cells

Potency in cells:

IC50

44 nM (I), 40 nM (C), 20 nM (P), 128 nM (W)

Potency assay (cells):

Inhibition of IL-6–induced phosphorylation of STAT3 in cell (I) and Whole Blood (W), Chemokine MCP-1 production (C), Inhibition pSTAT3 stimulated by IL-23 (P), Cell Proliferation Inhibition

In vivo validation

Organism:

Mouse, Rat

Dose:

1, 3, 10 mg/Kg

Route of delivery:

Oral

Primary Reference

Reference (doi):

10.4049/jimmunol.0902819 10.1016/j.str.2015.12.015

Reference (PMID):

20363976 26853940

Baricitinib

Probe Availability

Probe Information

Target Details

Janus kinase 1, JAK1AB, JTK3, JAK1, Janus kinase 2, JTK10, THCYT3

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Baricitinib

Probe Availability

Probe Information

Target Details

Janus kinase 1, JAK1AB, JTK3, JAK1, Janus kinase 2, JTK10, THCYT3

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?