SGC-SMARCA-BRDVIII

Protein target name:

SMARCA2, SMARCA4, PBRM1

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 10 uM

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Bromodomain

HUGO ID:

HGNC:11098 HGNC:11100 HGNC:30064

Entrez gene ID:

6595 6597 55193

UNIPROT ID:

P51531 P51532 Q86U86

Target alias:

BRM; SNF2; SWI2; hBRM; NCBRS; Sth1p; BAF190; SNF2L2; SNF2LA; hSNF2a; BRG1; CSS4; SNF2; SWI2; MRD16; RTPS2; BAF190; SNF2L4; SNF2LB; hSNF2b; BAF190A; SNF2-beta; PB1; BAF180

Probe Details

Chemical Probes Portal ID:

CPP2239

Probe alias:

cpd 22, QP8

PubChem CID:

137045929

SMILES string:

OC1=CC=CC=C1C2=CC(N3CCN(C(OC(C)(C)C)=O)CC3)=C(N)N=N2

InChi Key:

AQTNUGRRZDRZIA-UHFFFAOYSA-N

Control compound:

SGC-BRDVIII-NC

Orthogonal probe:

PFI-3

Physico-chemical properties

NMR:

1H NMR (500 MHz, DMSO-d6): δ [ppm] 10. 96 (br s, 1H, OH), 9.84 (s, 2H, piperazine-NH·HCl), 7.79 (br s, 3H, NH2·HCl), 7.62 (s, 1H, pyridazine-CH), 7.57 (d, J = 7.5 Hz, 1H, phenol-CH-3), 7.37 (t, J = 7.5 Hz, 1H, phenol-CH-5), 7.15 (d, J = 8.1 Hz, 1H, phenol-CH-6), 6.96 (t, J = 7.4 Hz, 1H, phenol-CH-4), 3.47 (br s, 4H, piperazine-2(CH2)-2), 3.32 (br s, 4H, piperazine-2(CH2)-3);

13C NMR (125 MHz, DMSO-d6): δ [ppm] 155.6, 132.2, 129.9, 119.5, 116.7, 45.4, 41.8

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

SMARCA2 35 nM, SMARCA4 36 nM, PBRM1 13 nM

Potency assay:

ITC

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

6ZS4

Structure-activity relationship:

yes

Off target activity

Potency (off target):

Off target protein and potency:

PB1(2) 3655 nM, PB1(3) 1963 nM

Probe Selectivity in Vitro:

Selectivity of the SGC-SMARCA-BRDVIII probe within the bromodomain families was confirmed by an in-house thermal shift panel containing 25 bromodomains. Outside Target Family: No activity was also observed on 85 protein kinases screened in an in-house DSF panel.

In cell validation

On target activity in cells

Potency in cells:

EC50

< 1 uM

Potency assay (cells):

adipogenesis cell differentiation assay

Off target activity in cells

Probe Selectivity in Cell:

SGC-SMARCA-BRDVIII is non-toxic and does not influence cell growth at a dose of 10 µM as indicated in the NCI-60 human tumor cell lines screen, and can therefore ideally used in cell differentiation assays.

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

No Toxicity detected at 10 uM

Primary Reference

Reference (doi):

10.1021/acs.jmedchem.0c01242

Reference (PMID):

33216538

External Resources

Available data:

SGC Chemical Probes

SGC-SMARCA-BRDVIII

Probe Information

Target Details

BRM; SNF2; SWI2; hBRM; NCBRS; Sth1p; BAF190; SNF2L2; SNF2LA; hSNF2a; BRG1; CSS4; SNF2; SWI2; MRD16; RTPS2; BAF190; SNF2L4; SNF2LB; hSNF2b; BAF190A; SNF2-beta; PB1; BAF180

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

External Resources

Supporting Organizations

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SGC-SMARCA-BRDVIII

Probe Information

Target Details

BRM; SNF2; SWI2; hBRM; NCBRS; Sth1p; BAF190; SNF2L2; SNF2LA; hSNF2a; BRG1; CSS4; SNF2; SWI2; MRD16; RTPS2; BAF190; SNF2L4; SNF2LB; hSNF2b; BAF190A; SNF2-beta; PB1; BAF180

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?