ACBI1

Degrader (PROTAC) of SMARCA2, SMARCA4, PBRM1

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe ACBI1 is in the process of SERP review.

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Information

SMARCA2
SMARCA4
PBRM1

Degrader (PROTAC)

up to 1 uM

DOI - 10.1038/s41589-019-0294-6

Probe Availability:

In Vitro Validations

Uniprot ID: P51531

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50, Ki

Potency Value: 770 nM Binary; 26 nM Ternary; 450 nM Binary (Ki); 16 nM Ternary (Ki)

Potency Assay: Fluorescence Polarization competition assays, TR-FRET assay, SPR

PDB ID for probe-target interaction (3D structure): 6HAX

Structure-activity relationship: yes

Target aliases:

Probable global transcription activator SNF2L2, SN ...

DOI Reference: 10.1038/s41589-019-0294-6

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): Mass Spectrometry

Probe Selectivity in Cell:

Effects of ACBI1 and cis-ACBI1 @ 333 nM for 8 h on the proteome of MV-4-11 cells were assessed by MS. Significant knockdown of SMARCA2, SMARCA4 and PBRM1 effects with minimal down-regulation of other proteins across the proteome was observed.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

ACBI1 is a well characterized and potent degrader for SMARCA2/4 and PBRM1. Researchers demonstrate proteome selectivity and a target-dependent phenotypic response in multiple AML cell lines. The probe is also shown to deplete other BAF complex subunits likely due to their inability to interact with SMARCA2/4 and PBRM1, demonstrating the potential for chemical mediated manipulation of the BAF/PBAF complex. Future investigation into the modest potency of the diastereomer negative control in NCI-H1568 cells would be beneficial.

(last updated: 2 Nov 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

This is a well-characterized chemical probe that degrades SMARCA2/4, PBRM1 of the SWI/SNF complex. Based on proteomics data, it does not degrade the other components of the complex. A dose-response (not exceeding 1 micromolar) will provide more evidence of an on-target effect. If possible confirm the phenotype with one of the bromodomain antagonists.

(last updated: 2 Nov 2021 )