MS436

Protein target name:

BRD4, BRD3

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 10 uM

Probe Availability

MedChemExpress

TOCRIS

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Bromodomain

HUGO ID:

HGNC:13575 HGNC:1104

Entrez gene ID:

23476 8019

UNIPROT ID:

O60885 Q15059

Target alias:

CAP, HUNK1, HUNKI, MCAP, ORFX, RING3L

Probe Details

Chemical Probes Portal ID:

CPP1311

Probe alias:

MS-436; cpd27, NUD

PubChem CID:

60171585

ChEMBL ID:

CHEMBL3086883

SMILES string:

O=S(C1=CC=C(/N=N/C2=CC(C)=C(O)C=C2N)C=C1)(NC3=NC=CC=C3)=O

InChi Key:

BBJDRANVVNBXAR-JWGURIENSA-N

Orthogonal probe:

MZ1dBET6AT1

PAINs evaluation:

Yes, this molecule contains PAINS and Toxicophores

Physico-chemical properties

NMR:

1H NMR (600 MHz, DMSO-d6) δ 10.28 (br s, 1H), 7.98 (m, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.71 (t, J = 7.2 Hz, 2H), 7.37 (s, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.11 (br s, 2H), 6.85 (t, J = 6.0 Hz, 1H), 6.22 (s, 1H), 2.00 (s, 3H).

13C NMR (150 MHz, DMSO-d6) δ 162.0, 155.4, 153.7, 147.0, 141.0, 138.2, 133.2, 131.3, 128.7, 128.2, 121.9, 115.4, 114.4, 103.4, 100.4, 15.7.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

85 nM BD1, 340 nM BD2

Potency assay:

in vitro fluorescent anisotropy binding assay

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

4NUD

Structure-activity relationship:

yes

Off target activity

Potency assay (off target):

in vitro fluorescent anisotropy binding assay

Probe Selectivity in Vitro:

Selectivity against a panel of Bromodomains (Ki - uM): BRD4-BD2 0.34, BRD3-BD1 0.10, BRD3-BD2 0.14; related targets, BRD2 and BRDT were not tested, but are likely to bind MS436; CBP BD 2.18, PCAF 5.52, BRD7 2.72, BPTF 6.06, BAZ2B 3.29, SMARCA4 7.97

In cell validation

On target activity in cells

Potency in cells:

IC50

4.9 uM (ELISA), 3.8 nM (NO)

Potency assay (cells):

Inhibition of NF-κB pathway (NO assay), ELISA assay

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

MTT assay in RAW264.7 cells @ 100 uM shows little cytotoxicity

Primary Reference

Reference (doi):

10.1021/jm401334s

Reference (PMID):

24144283

MS436

Probe Availability

Probe Information

Target Details

CAP, HUNK1, HUNKI, MCAP, ORFX, RING3L

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

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MS436

Probe Availability

Probe Information

Target Details

CAP, HUNK1, HUNKI, MCAP, ORFX, RING3L

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

Interested in supporting the portal?