GDC-0834

Protein target name:

BTK

Mechanism of action:

InhibitorATP competitive

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

MedChemExpres

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

HUGO ID:

HGNC:1133

Entrez gene ID:

695

UNIPROT ID:

Q06187

Target alias:

Bruton tyrosine kinase, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA

Probe Details

Chemical Probes Portal ID:

CPP1212

Probe alias:

GDC 0834, GDC0834, 2VL, cpd2

PubChem CID:

25234918

ChEMBL ID:

CHEMBL2057915

SMILES string:

O=C(C1=CC(CCCC2)=C2S1)NC3=CC=CC(C(N=C4NC5=CC=C([C@H]6N(C)CCN(C)C6=O)C=C5)=CN(C)C4=O)=C3C

InChi Key:

CDOOFZZILLRUQH-GDLZYMKVSA-N

Orthogonal probe:

CGI1746AVL-252

Physico-chemical properties

NMR:

1H NMR (300 MHz, DMSO-d6) d 9.78 (s, 1 H), 9.20 (s, 1 H), 7.89 (d, 2 H, J = 8.4 Hz), 7.66 (s, 1 H), 7.28-7.32 (m, 3 H), 7.18 (s, 1 H), 7.14 (d, 2 H, J = 8.4 Hz), 3.93 (s, 1 H), 3.57 (m, 1 H), 3.53 (s, 3 H), 3.20 (d, 1 H, J = 11.7 Hz), 2.93 (d, 1 H, J = 11. 1 Hz), 2.80 (s, 3 H), 2.73 (m, 2 H), 2.59 (m, 2 H), 2.54 (m, 1 H), 2.26 (s, 3 H), 2.01 (s, 3 H), 1.75 (m, 4 H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

6 nM

Potency assay:

assayed at Invitrogen using the Z'-LYTE platform, Lanthascreen

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

4OTF

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

excellent biochemical selectivity against a panel of 331 kinases, except for TEC-family kinase Bmx where a 3-fold difference was observed.

In cell validation

On target activity in cells

Potency in cells:

EC50

60 nM CD86, 350 nM CD63, 380 nM CD69

Potency assay (cells):

cell based CD86 assay, whole blood inhibition of both anti-IgE stimulated CD63 expression and anti-IgD stimulated CD69 expression

Off target activity in cells

Probe Selectivity in Cell:

Minimal to no off-target receptor activity when screened against a panel of 30 targets (all <35% at 10 μM), minimal inhibition of the hERG channel (27% at 10 μM), and was negative in a gene-tox profile Ames (TA98/100 strains; +/− S9) and micronucleus tests (+/− S9). Known to bind six AO substrates with IC50 values ranging from 0.86 to 1.87 μM.

In vivo validation

Organism:

Female Lewis rats BALB/c mice

Dose:

30-100 mg/Kg

Route of delivery:

Oral

Systemic clearance:

4.4 mL/min/Kg

Primary Reference

Reference (doi):

10.1016/j.bmcl.2015.01.032 10.1124/jpet.111.181545 10.1124/dmd.114.061804

Reference (PMID):

25701252 21521773 25845827

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

This compound was shown to be a substrate and inhibitor of human aldehyde oxidase. It is a good tool compound to use in cells and small animals, but there are marketed BTK inhibitors that would be more appropriate for routine experiments because they do not interact with AO.

Jun 4 2021 - 11:46am

At higher concentrations (3-10 uM) this compound has off-target activities in human primary cell assays that may confound interpretation of results in phenotypic assays or animal studies. These activities include inhibition of proliferation of human primary endothelial cells, T cells, coronary artery smooth muscle cells and fibroblasts.

Jun 25 2021 - 4:56pm

GDC-0834

Probe Availability

Probe Information

Target Details

Bruton tyrosine kinase, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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GDC-0834

Probe Availability

Probe Information

Target Details

Bruton tyrosine kinase, AGMX1, AT, ATK, BPK, IMD1, PSCTK1, XLA

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?