ACBI1

Degrader (PROTAC) of SMARCA2, SMARCA4, PBRM1

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

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 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

Very good probe and an excellent tool to study the BAF chromatin remodelling complex. Provides details on the reliance of its ATPase domains to form the full complex structure. Meets most criteria for a good PROTAC however, no Dmax was determined and neither was a 'Hook' effect concentration. Some issues may also arise with toxicity if studied in-vivo as embryonic death occurs in mice as a result of loss of SMARCA4.

(last updated: 6 Feb 2026 )