PFI-4

PFI-4 : Inhibitor of BRPF1

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

BRPF1 (Other variant:Isoform B)

Inhibitor

up to 1 uM

Additional Data

SGC Chemical Probe Collection

Probe Availability:

In Vitro Validations

Uniprot ID: P55201

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 13 nM

Potency Assay: ITC

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

Target aliases:

Peregrin, BR140, BRPF1, BRPF1_HUMAN, Protein Br140 ...

DOI Reference: 10.1021/ml5002932

Uniprot ID: P55201

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 172 nM

Potency Assay: Alpha Screen competitive assay with tetraacetylated histone 4 and monoacetylated K14 histone 3 for TRIM24.

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

Target aliases:

Peregrin, BR140, BRPF1, BRPF1_HUMAN, Protein Br140 ...

DOI Reference: 10.1021/ml5002932

Uniprot ID: P55201

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: ΔTm

Potency Value: 9.4 Celciuys

Potency Assay: Thermal Shift assay

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

Target aliases:

Peregrin, BR140, BRPF1, BRPF1_HUMAN, Protein Br140 ...

DOI Reference: 10.1021/ml5002932

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

PFI-4 induced significant temperature shifts for BRPF1B (ΔTm of 9.4 °C). Weak interactions (2.0 °C) were also observed for BRD1 and CECR2, however the binding to BRD1 shows 60-fold selectivity with a KD of 775 nM and IC50 of 3600 nM. CECR2 was the only detected off-target outside family IV with only 2350 nM affinity (Kd), thus showing 167-fold selectivity.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

Recommended for in vitro studies at a 1 uM concentration. No PK data available so not recommended for in vivo studies without first determining the PK profile.

(last updated: 19 Jul 2022 )

SERP Ratings

In Cell Rating

SERP Comments:

A structurally negative control compound has not been recommended in the publication. Pan-BRPF bromodomain inhibitors (OF-1, NI-57) led to similar phenotypes in specific model systems. CECR2 is an off-target around 2 µM in-vitro. For cellular studies a CECR2 probe could be used as a control to dissect effects (https://www.thesgc.org/chemical-probes/NVS-CECR2-1)

(last updated: 2 Aug 2022 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

The selectivity of this compound is very good, but a negative control is missing. No in vivo efficacy has been established and no DMPK data are available.

(last updated: 22 Mar 2023 )