Using these assays, we screened approximately 1700 compounds, and identified novel ligands for TRIM24, TRIM33α, and TRIM33β. We also show that the compounds disclosed in a recent patent do not bind to TRIM33β in our hands. This work provides the foundation for the development of more refined TRIM33 ligands, which will enable the function of this fascinating protein to be further explored, and potentially recruited as an E3 ligase in proteolysis-targeting chimeras (PROTACs). To determine whether TRIM33 is of potential interest as a therapeutic target in oncology, we compared the expression levels of TRIM33 in a range of cancer and non-cancer cell lines using western blotting (Figure ). We demonstrate that the cancer cell lines generally show higher expression levels of both TRIM33, and ALC-1 compared to related non-cancer cell lines. ALC1 is a helicase that is recruited to the site of single strand breaks (SSBs) through binding of its macrodomain to poly(ADP-ribose) (PAR). Its helicase activity relaxes the chromatin structure to allow repair, but this activity is short-lived (t ½ ≈ 2.5 min) and tightly regulated as prolonged chromatin relaxation exposes it to further damage. TRIM33 is recruited to the site of SSBs in an ALC1-dependent manner, and is required to ensure timely dissociation of ALC1 from chromatin. TRIM33 does not bind PAR directly, but deletion of the chromatin-binding PHD/BRD module prevents TRIM33 localisation to sites of laser scissor-induced DNA breaks. TRIM33 (sh/siRNA) knock down studies conducted by Kulkarni et al. showed accumulation of ALC1 at the sites of DNA damage, evidence of DNA damage-induced checkpoint activation, and prolonged DNA damage. Combined with our data, these observations raise the possibility that inhibition of TRIM33 BRD and/or PHD function might be of therapeutic benefit in cancers that have high levels of TRIM33. These data encouraged us to identify ligands for the TRIM33 BRD and PHD to probe their functions.