SPEN-IN-1 (compound X1) is an inhibitor of SPEN which is a protein factor with a Kd value of 47 nM. SPEN-IN-1 has high selectivity for RepA, a 431-nucleotide domain in Xist (a non-coding RNA prototype) that comprises 8.5 units of a GC-rich motif responsible for gene silencing[1].
SPEN-IN-1 (0-100 μM) 抑制 RepA-PRC2 和 RepA-SPEN，IC50 值分别为 30 和 48 μM[1]。
SPEN-IN-1 抑制 RepA、PRC2 和 SPEN，Kd 值分别为 400、47 和 420 nM[1]。
SPEN-IN-1 在体外和细胞内选择性地破坏 Xist 与同源蛋白的相互作用[1]。
SPEN-IN-1 强烈抑制 H3K27me3 和 PRC2 的积累[1]。
SPEN-IN-1 减少 RepA-SPEN 的体内相互作用[1]。
[1]. Aguilar R, et al. Targeting Xist with compounds that disrupt RNA structure and X inactivation. Nature. 2022 Apr;604(7904):160-166.