GDC-0834

Protein target name:

BTK

Mechanism of action:

InhibitorATP competitive

Probe Availability

MedChemExpres

Probe Information

Target and Probe Information

Target Details

Target class:

Protein kinase

Subclass:

Tyrosine kinase

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

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

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?

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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?