GSK2801

Protein target name:

BAZ2A, BAZ2B

Mechanism of action:

Antagonist

Probe Availability

MedChem Express (1619994-68-1)

Tocris (1619994-68-1)

Abcam (1619994-68-1)

Cayman (1619994-68-1)

MilliporeSigma (GSK2801)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Bromodomain

HUGO ID:

HGNC:962 HGNC:963

Entrez gene ID:

11176 29994

UNIPROT ID:

Q9UIF9 Q9UIF8

Target alias:

TIP5, WALp3, WALp4

Probe Details

Chemical Probes Portal ID:

CPP65

Probe alias:

KB-146016

PubChem CID:

73010930

SMILES string:

CCCOC1=CC2=C(C=C(N2C=C1)C(=O)C)C3=CC=CC=C3S(=O)(=O)C

InChi Key:

KHWCPNJRJCNVRI-UHFFFAOYSA-N

Control compound:

GSK8573, with activity against BRD9

Orthogonal probe:

BAZ2-ICR

Physico-chemical properties

NMR:

1H NMR (400 MHz, chloroform-d) δ ppm 1.04 (t, J = 7.28 Hz, 3 H),
1.70−1.92 (m, 2 H), 2.57 (s, 3 H), 2.68 (s, 3 H), 3.89 (t, J = 6.27 Hz,
2 H), 6.60 (s, 1 H), 6.68 (d, J = 7.53 Hz, 1 H), 7.51 (d, J = 7.28 Hz, 1 H),
7.56−7.64 (m, 1 H), 7.67−7.74 (m, 1 H), 7.81 (s, 1 H), 8.34 (d, J = 7.78
Hz, 1 H), 9.81 (d, J = 7.53 Hz, 1 H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

BAZ2A 257 nM, BAZ5B 136 nM

Potency assay:

Isothermal calorimetry and Biolayer interferometry. In biochemical FRET assays, IC50s were BAZ2A=0.4 uM and BAZ2B=0.43 uM.

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

4RVR

Structure-activity relationship:

Yes

Off target activity

Potency (off target):

Off target protein and potency:

TAF1L(2) 0.32 uM, BRD9 1.1 uM

Potency assay (off target):

Thermal stability assays. Of 42 Bromodomains tested, GSK2801 was only active against BRD9 and TAF1L

Probe Selectivity in Vitro:

Unknown

In cell validation

On target activity in cells

Potency assay (cells):

In a cellular FRAP assay (U2OS cells), 1 uM GSK2801 displaced GFP-BAZ2A from acetylated chromatin.

Target engagement assay (cells):

Yes, in cell FRAP assay (indirect) and chemoproteomics (direct)

In vivo validation

Organism:

CD1 mouse

Dose:

30 mg/kg

Route of delivery:

OralIntraperitoneal

Plasma half life:

4.5 h (IP)1.5 h (oral)

Cmax:

1,670 ng/mL (IP)435 ng/mL (oral)

Tmax:

0.25 h (IP)1 h (oral)

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.5b00209

Reference (PMID):

25799074

GSK2801

Probe Availability

Probe Information

Target Details

TIP5, WALp3, WALp4

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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GSK2801

Probe Availability

Probe Information

Target Details

TIP5, WALp3, WALp4

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?