I-BRD9

Antagonist of BRD9

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(0 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

BRD9

Antagonist

DOI - 10.1021/acs.jmedchem.5b00256

Probe Availability:

In Vitro Validations

Uniprot ID: Q9H8M2

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: pIC50

Potency Value: BRD9 7.3

Potency Assay: TR-FRET, and BROMOscan profiling with N-methyl Kac mimetic: BRD9 pKD = 8.7.

PDB ID for probe-target interaction (3D structure): 4UIW

Structure-activity relationship: Yes

Target aliases:

Bromodomain-containing protein 9, BRD9, BRD9_HUMAN ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : pIC50 BRD4 5.3

Potency assay (off target): In TR-FRET assay, I-BRD9 is 100-fold selective for BRD9 > BRD4. In BROMOscan profiling (DiscoveRx), I-BRD9 is >70-fold selective for BRD9 (pKD = 8.7) compared with 34 bromodomains, including BRD7 (pKD = 6.4, 200-fold), showing >700-fold selectivity for BRD9 over BET bromodomains.

Probe Selectivity in Vitro:

There was no activity detected with < 5 uM I-BRD9 against 49 receptors, transporters, ion channels or kinases.

Probe Selectivity in Cell:

>625-fold selective for BRD9 > BRD3 in HUT-78 cells.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The I-BRD9 small molecule is a selective BRD9 inhibitor (binding activity by TR-FRET assay with pIC50 = 7.3, NanoBRET pIC50 = 6.8) identified through structure-based design. This compound is selective for BRD9 over BRD7 (200-fold), over the BET family > 700-fold, and >70-fold against a panel of 34 bromodomains. This compound is soluble and permeable: ChromLogD (pH7.4) = 3.7, aqueous solubility (CLND) = 359 μM, and artificial membrane permeability = 210 nm/s. The selectivity over BRD7 has allowed scientists to explore the phenotypic effects of inhibiting BRD9.

(last updated: 10 Aug 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

I-BRD9 shows >50-500 fold selectivity vs. various targets such as BET and other relevant bromo-domains.

(last updated: 10 Aug 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

I-BRD9 is a potent inhibitor of BRD9 (pIC50 = 7.3, IC50 = 50 nM) with >700-fold selectivity over the BET family, 200-fold selectivity over BRD7, 100-fold selectivity over BRD4 BD1 (pIC50 = 5.3, IC50 = 11 nM) and >70-fold selectivity over all other bromodomains. It is active in a cellular BRD9 NanoBRET assay (pIC50 = 6.8, IC50 = 158 nM). The binding mode of I-BRD9 to BRD9 is determined by X-ray crystallography.

(last updated: 10 Sept 2016 )