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^[1]. EED226 is a potent, selective, and orally bioavailable EED inhibitor^[2]. EED226 inhibitsPRC2with anIC₅₀of 23.4 nM when the H3K27me0 peptide is used as a substrate in the in vitro enzymatic assays^[3].

IC50: 23.4 nM (PRC2)^[3]

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^-6cm/s, with an efflux ratio at 7.6^[2].
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× K_act(1.0 μM)^[3].

EED226 induces robust and sustained tumor regression in EZH2^MUTpre-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 lowin vivoclearance, 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)^[2].

369.40

Solid

C₁₇H₁₅N₅O₃S

2083627-02-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 125 mg/mL(338.39 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 0.5%HPMC  1%Tween80

  Solubility: 10 mg/mL (27.07 mM); Suspened solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (6.77 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.77 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (6.77 mM); Suspended solution

  此方案可获得 ≥ 2.5 mg/mL (6.77 mM，饱和度未知) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (6.77 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.77 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。