EED226 is a potent inhibitor of Polycomb repressive complex 2 (PRC2) with an IC50 value of 22.3nM [1]. EED226 binds to the H3K27Me3 binding pocket of EED through a allosteric mechanism, thereby inhibiting the function of PRC2. It effectively suppresses the level of H3K27Me3 in the cell and regulates the expression of target genes. [2]. EED226 has been widely used in cell and animal models to inhibit tumor progression[3].
In vitro, EED226 treatment for 5 days significantly inhibited the proliferation of NGP and IMR32 cells, with IC50 values of 2.64μM and 2.05μM, respectively[4]. EED226 treatment at 5μM for 48 hours significantly enhanced the proliferation of female germline stem cells (FGSCs), promoted the expression of OCT4, and inhibited the expression of P53 and P63[5].
In vivo, EED226 treatment via daily intragastric administration (40mg/kg) twice for 2 days improved renal function and alleviated renal injury in the mouse model of acute kidney injury (AKI) induced by cisplatin[6]. Oral administration of EED226 twice daily (40mg/kg) for 32 days can inhibit tumor growth in the Karpas422-xenograft mouse models[7]. Oral administration of EED226 twice daily (40mg/kg) for 30 days effectively alleviated the symptoms of experimental autoimmune encephalomyelitis (EAE) in mice and improved inflammatory infiltration[8].
References:
[1] Cook N, Chen J, Zhou J, et al. Embryonic ectoderm development (EED) as a novel target for cancer treatment[J]. Current topics in medicinal chemistry, 2021, 21(31): 2771-2777.
[2] Liu K L, Zhu K, Zhang H. An overview of the development of EED inhibitors to disable the PRC2 function[J]. RSC Medicinal Chemistry, 2022, 13(1): 39-53.
[3] Atadja P W. Abstract IA19: Targeting the PRC2 complex through EED for anti-cancer therapy[J]. Cancer Research, 2017, 77(22_Supplement): IA19-IA19.
[4] Shaliman D, Takenobu H, Sugino R P, et al. The PRC2 molecule EED is a target of epigenetic therapy for neuroblastoma[J]. European Journal of Cell Biology, 2022, 101(3): 151238.
[5] Wang J, Fang J, Feng M, et al. Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro[J]. Open Biology, 2023, 13(1).
[6] Yu C, Li T, Li J, et al. Inhibition of polycomb repressive complex 2 by targeting EED protects against cisplatin‐induced acute kidney injury[J]. Journal of Cellular and Molecular Medicine, 2022, 26(14): 4061-4075.
[7] Qi W, Zhao K, Gu J, et al. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED[J]. Nature chemical biology, 2017, 13(4): 381-388.
[8] Hong W, Ma H, Li Z, et al. Inhibition of EED-mediated histone methylation alleviates neuroinflammation by suppressing WNT-mediated dendritic cell migration[J]. Journal of Neuroinflammation, 2025, 22(1): 97.
EED226是一种强效的多梳抑制复合物2（PRC2）抑制剂，IC50值为22.3nM[1]。EED226通过变构机制结合到EED的H3K27Me3结合口袋，从而抑制PRC2的功能，能有效降低细胞中H3K27Me3的水平，并调控靶基因的表达[2]。EED226已被广泛用于细胞和动物模型中抑制肿瘤进展[3]。
在体外，EED226处理5天显著抑制了NGP和IMR32细胞的增殖，IC50值分别为2.64μM和2.05μM[4]。使用5μM的EED226处理48小时，显著增强了雌性生殖干细胞（FGSCs）的增殖，促进了OCT4的表达，并抑制了P53和P63的表达[5]。
在体内，每日两次灌胃给予EED226（40mg/kg），连续2天，改善了顺铂诱导的急性肾损伤（AKI）小鼠模型中的肾功能，并减轻了肾损伤[6]。每日两次口服EED226（40mg/kg），连续32天，可抑制Karpas422细胞异种移植小鼠模型中的肿瘤生长[7]。每日两次口服EED226（40mg/kg），连续30天，有效减轻了小鼠实验性自身免疫性脑脊髓炎（EAE）的症状，并改善了炎症浸润[8]。