EED226 是一种多梳抑制复合物 2 (PRC2) 抑制剂，与胚胎外胚层发育 (EED) 上的 K27me3 口袋结合，在移植瘤小鼠模型中具有强的抗肿瘤活性。EED226 是一种有效的，口服可生物利用的，选择性 EED 抑制剂。当 H3K27me0 肽用作体外酶法测定的底物时，EED226 抑制 PRC2 的 IC₅₀ 为 23.4 nM。

EED226 is a polycomb repressive complex 2 (PRC2) inhibitor, which binds to the K27me3-pocket on embryonic ectoderm development (EED) and shows strong antitumor activity in xenograft mice model. EED226 is a potent, selective, and orally bioavailable EED inhibitor. EED226 inhibits PRC2 with an IC 50 of 23.4 nM when the H3K27me0 peptide is used as a substrate in the in vitro enzymatic assays.

Solid

IC50: 23.4 nM (PRC2)

EED226 is a highly potent, efficient and selective inhibitor of EZH2 and EZH1 evaluated against a broad range of epigenetic and non-epigenetic targets. It potently reduces global H3K27Me3 mark in cells and demonstrates selectively cell killing effects in cells carrying a heterozygous Y641N mutation. EED226 has moderate permeability as the measured in Caco-2 cells at A→B=3.0x10 cm/s, with an efflux ratio at 7.6.
In the in vitro enzymatic assays, EED226 inhibited PRC2 with an IC50 of 53.5 nM when the mononucleosome is used as the substrate, with the stimulatory H3K27me3 added at 1× Kact (1.0 μM). has not independently confirmed the accuracy of these methods. They are for reference only.

EED226 induces robust and sustained tumor regression in EZH2 pre-clinical DLBCL model. In CD-1 mice, dosing of EED226 for 14 days at 300 mg/kg bid is well tolerated with no apparent adverse effects. It has very low in vivo clearance, and approximately 100% oral bioavailability. EED226 has low volume of distribution (0.8 L/kg), reasonable terminal t 1/2 (2.2 h), and moderate plasma protein binding (PPB). has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Li L, et al. Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED. PLoS One. 2017 Jan 10;12(1):e0169855.
[2]. Huang Y, et al. Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy. J Med Chem. 2017 Mar 23;60(6):2215-2226.

In Vitro: DMSO : ≥ 125 mg/mL (338.39 mM)配制储备液