BAY-299

Antagonist of BRD1, TAF1, TAF1L

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 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

BRD1
TAF1
TAF1L

Antagonist

2-500 nM

DOI - 10.1021/acs.jmedchem.7b00306

Probe Availability:

In Vitro Validations

Uniprot ID: O95696

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC 50

Potency Value: 67 nM

Potency Assay: Time-resolved fluorescence resonance energy transfer (TR-FRET) assay

PDB ID for probe-target interaction (3D structure): 5N49

Structure-activity relationship: The primary publication lists SAR of position 6, 5', and 6' of the 1,3-dimethyl-benzimidazolone core and naphthalimide moiety, respectively. Position 6 SAR was done to optimize for BRPF2 BD, BRPF1 BD, TAF1 BD2 and BRD4 BD1 activity while position 5' and 6' were used to optimize BRPF2 BD, BRPF1 BD, TAF1 BD2 and BRD4 BD1 activity. Another SAR was done to improve solubility. TF-FRET was used to generate all SAR.

Target aliases:

Bromodomain-containing protein 1, BRPF2, BRL, BRD1 ...

DOI Reference: 10.1021/acs.jmedchem.7b00306

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : Kd 1,390 nM

Potency assay (off target): Thermal Shift Assay on a panel of 48 bromodomains and BROMOscan panel.

Probe Selectivity in Vitro:

LeadProfilingScreen (Cerep) containing 68 potential protein targets at 10 uM, with no inhibition or stimulation >25% observed. At 10 uM, BAY-299 showed <50% inhibitory activity in a panel of 300 kinases for all proteins. Thermal Shift Assay on a panel of 48 bromodomains and BROMOscan panel.

Potency assay, off target (cells): NanoBRET

Probe Selectivity in Cell:

BAY-299 showed no activity against BRD4-H4 or BRPF1-H4 in NanoBRET assays up to 10 uM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

As the compound showed similar binding affinity between two type of Bromo domains (BDs) from two proteins with very different roles in transcriptional regulation means that it is not amenable for use as a chemical probe to investigate the functions of these types of BDs.

(last updated: 21 Jun 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Cellular data show activity of BAY-299 on BRPF2 BD/H3.3, BRPF2 BD/H4, TAF1 BD2/H3.3, and TAF1 BD2/H4. However, little or no anti-proliferative affect was detected.

(last updated: 30 Jun 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Because the compound showed similar binding affinity for two types of Bromodomains (BDs) from two proteins with very different roles in transcriptional regulation, it is not amenable for use as a chemical probe to investigate the functions of these types of BDs.

(last updated: 28 Jul 2017 )