dTRIM24

dTRIM24 is a selective bifunctional degrader of TRIM24 based on PROTAC.

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

Signaling Pathways >> PROTAC >> PROTAC

Research Areas >> Cancer

TRIM24[2].

dTRIM24 is a degrader of TRIM24 bromodomain. Recruitment of the VHL E3 ubiquitin ligase by dTRIM24 elicits potent and selective degradation of TRIM24. The anti-proliferative consequences of chemical degradation versus inhibition of TRIM24 are assessed. Growth over time is determined for MOLM-13 cells treated with dTRIM24, IACS-9571, VL-269, and eTRIM24. dTRIM24 suppresses growth to a greater extent than does IACS-9571, accompanied by apoptosis measured as enhanced PARP cleavage. In agreement with a sustained proliferative defect observed following dTRIM24 treatment, near-complete degradation of TRIM24 is observed in dTRIM24-treated cells throughout the duration of the experiment[2].

MOLM-13 cells are seeded at 30,000 cells/well. Growth over time of MOLM-13 cells treated with 5 μM of indicated compounds (e.g., dTRIM24) over 7 d. At endpoints, cells are suspended and mixed with Viacount reagent at 1:3. The mixture is incubated for 5 min, and viable cells are counted on the Guava easycyte flow cytometer. Means from three technical replicates of cell counts are calculated[2].

[1]. Gechijian LN, et al. Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat Chem Biol. 2018 Apr;14(4):405-412.

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