dTRIM24

dTRIM24 : Degrader (PROTAC) of TRIM24

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe dTRIM24 is in the process of SERP review.

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Information

TRIM24

Degrader (PROTAC)

~~5 uM~~
Reviewer recommended concentration: 2.5 to 5 uM

DOI - 10.1038/s41589-018-0010-y

Probe Availability:

In Vitro Validations

Uniprot ID: O15164

Target Class: Epigenetic

Target SubClass: Tripartite Motif Family

Potency: IC50

Potency Value: 338 nM

Potency Assay: TRIM24 ligand-displacement assay

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

Structure-activity relationship: no

Target aliases:

Transcription intermediary factor 1-alpha, TIF1A, ...

DOI Reference: 10.1038/s41589-018-0010-y

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency end-point : KD BRD1 130 nM, BRPF1 52 nM

Potency assay (off target): BromoScan

Probe Selectivity in Vitro:

dTRIM24 in vitro binding assay to panel of human bromodomain proteins by single-point screening at 1 μM dTRIM24 in singlicate

Probe Selectivity in Cell:

Outside target family: Proteomics analysis of MCF-7 cells

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

dTRIM24 is a high-quality targeted degrader of TRIM24. It has been subjected to many of the best-available TPD validation experiments where it shows: potent and elective biochemical target engagement to TRIM24, cellular permeability, proteasome dependence, VHL dependence, selective cellular TRIM24 degradation, activity in multiple cell models, and others.

Recommend controls include the enantiomer eTRIM24, and even the IACS and VL building blocks.

The reported in vitro selectivity testing (BromoScan) indicates good cell-free selectivity (1 uM), and quantitative proteomics (2.5 uM, 4 h) demonstrated selective degradation of TRIM24 in cells.

While it appears dTRIM24 is sufficiently potent and selective, it would be prudent to further confirm:

1. Optimal dTRIM24 concentration and incubation time when using in different experimental conditions from the original report.

2. Selectivity versus select bromodomains when using in different experimental conditions from the original report.

(last updated: 9 Feb 2021 )

SERP Ratings

In Cell Rating

SERP Comments:

dTRIM24 is a potent and selective PROTAC molecule targeting TRIM24, which has been suggested as a dependency in numerous cancers. The dTRIM24 is formed by the conjugation of the TRIM24 ligand IACS-7e to the VHL ligand VL-269. This cell-permeable molecule has been reported to be selective against a panel of 32 human bromodomains showing a high binding ability, with a selectivity comparable to that reported for reference TRIM24 ligands (IACS-7e and IACS-9571). Its degradation activity has shown to be dependent on VHL and the proteasome. In particular, this chemical probe has been reported to have a potent degrading effect in MOLM-13 cells, a human acute myeloid leukaemia (AML) line.

(last updated: 18 Feb 2021 )