UNC-2170 is a functionally active, fragment-like ligand for 53BP1 (IC50=29 µM; Kd=22 µM). UNC-2170 shows at least 17-fold selectivity for 53BP1 as compared to nine other methyl-lysine (Kme) reader proteins. 53BP1 is a Kme binding protein that plays a central role in DNA Damage Repair (DDR) pathways and is recruited to sites of double-strand breaks (DSB)[1].
UNC-2170 (500 µM) results in a significant increase in soluble 53BP1 as compared to untreated lysates or lysates treated with UNC2892, the negative control compound. UNC-2170 (30-100 µM; naive splenocytes cultured with LPS and IL-4 for 3.5 days) clearly phenocopies the reduction in CSR seen in 53BP1 mutant B cells[1].
[1]. Perfetti MT, et al. Identification of a fragment-like small molecule ligand for the methyl-lysine binding protein, 53BP1. ACS Chem Biol. 2015;10(4):1072-1081.