kme readers

UNC-2170 (UNC2170 Maleate) 是53BP1(IC50=29 µM;Kd=22 µM) 选择性的、功能活性的片段状配体，对 53BP1 的选择性比其他九种甲基赖氨酸读取器蛋白质高出至少17倍。53BP1 是 Kme 结合蛋白，在 DNA 损伤修复途径中起核心作用，并被招募到双链断裂位点。

53BP1-binding protein 1 (53BP1) engages with dimethylated lysine 20 on histone 4 (H4K20me2) through its tandem tudor domains within a homodimer configuration, crucial for the DNA damage response. UNC2170, a micromolar 53BP1 ligand, selectively interacts with this site, demonstrating at least 17-fold preference for 53BP1 over similar proteins. This interaction occurs in a pocket formed by the 53BP1's tudor domains. Moreover, UNC2170 acts as an antagonist to 53BP1 in cellular lysates, effectively inhibiting class switch recombination, a process dependent on the functional 53BP1 tudor domain, thus confirming its cellular activity.