UNC3474 is a small molecule ligand, binding with 53BP1. UNC3474 binds the aromatic metl-lysine binding cage of 53BP1TT, with a dissociation constant (Kd) of 1.0 ± 0.3 μM. UNC3474 inhibits the recruitment of 53BP1 to DSBs by stabilizing a pre-existing autoinhibited state of 53BP1 in cells.
Unlike WT 53BP1TT, 53BP1TT-PN dose not interact with UNC3474[1].
References:
[1]. Cui G, et al. An autoinhibited state of 53BP1 revealed by small molecule antagonists and protein engineering. bioRxiv [Preprint]. 2023 Jul 18:2023.04.20.534960.