I-BET151

Antagonist of BRD4, BRD2, BRD3

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(2 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

BRD4
BRD2
BRD3

Antagonist

DOI - 10.1038/nature10509

Probe Availability:

In Vitro Validations

Uniprot ID: O60885

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 790 nM

Potency Assay: IC50 was measured in ligand-displacement assay

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

Target aliases:

Bromodomain-containing protein 4, HUNK1, BRD4, BRD ...

DOI Reference: 10.1038/nature10509

Uniprot ID: O60885

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 100 nM

Potency Assay: SPR

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

Target aliases:

Bromodomain-containing protein 4, HUNK1, BRD4, BRD ...

DOI Reference: 10.1038/nature10509

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

At 10 uM, I-BET151 had minimal activity (<40%) against a broad panel of pharmacologically active receptors, with the most activity against TACR2.

Probe Selectivity in Cell:

In a proteomic selectivity profile assessing HL60 cell nuclear extracts, I-BET151 had no effect on 23 off-target bromodomains other than BRD9.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

In a single-dose, mouse PK study (IP administration), I-BET-151 showed increased exposure and half-life compared to JQ1.

(last updated: 20 May 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

Due to the low potency of I-BET151, I would not recommend it as a cellular probe. More potent probes for BRD4 exist (e.g., JQ1 and I-BET762). None of these are selective for BRD4 though; they inhibit all of the BET family proteins with equal potency.

(last updated: 20 May 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

There are a number of well-characterized tool molecules available for the BRD2/3/4 family, and anyone seeking to use one of these probes is advised to consult the Chemical Probes Portal pages to view the latest molecules and data before selecting the appropriate probe. Across the probes listed, JQ1, PFI-1 as well as this I-BET151 are all broadly selective for the sub-family of BRD4-related bromodomains, with some evidence of cellular and in vivo activity. The relative levels of potency/activity are different across these assays. This molecule (like JQ1) is very well characterized, with wide selectivity building confidence that this probe will act on the BRD4-related bromodomains rather than on other targets. I-BET151 is less potent than other BET inhibitors such as JQ1, but it has better in vivo PK properties in mice.

(last updated: 27 Apr 2017 )