dTRIM24

dTRIM24 : Degrader (PROTAC) of TRIM24

Structure

Information

Protein target names: TRIM24

Mechanism of action: Degrader (PROTAC)

Recommended in-cell concentration:
5 uM

Reviewer recommended in-cell concentration: 2.5 to 5 uM

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

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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 )