Supplementary material. Identification of SET/EED dual binders as PRC2 innovative inhibitors.

Figure S1. 2D
chemical structure of the inhibitor
(3R,4S)-1-[(2-methoxyphenyl)methyl]-N,N-dimethyl-4-(1-methylindol-3-yl)pyrrolidin-3-amine
(LQD) co-crystallized in the embryonic ectoderm development (EED) model (PDB
ID 5U69).
Figure S2. 3D
representation of pharmacophore model in the binding pocket of EED. Chemical
features are color-coded: yellow, green and red spheres represent hydrophobic
features (HY), H-bond donors (HBD), and H-bond acceptors (HBA), respectively.
Figure S3. 2D
chemical structure of the S-Adenosyl-L-Homocysteine (SAM) co-crystallized in
the SET model (PDB ID 5HYN).
Figure S4. 3D
representation of pharmacophore model in the binding pocket of SET. Chemical
features are color-coded: yellow spheres represent hydrophobic features (HY),
green and red arrows represent H-bond donors (HBD) and H-bond acceptors
(HBA), respectively.
Figure S5. 2D
representation of the underlying binding interactions of the hit compounds A)
1, B) 2, C) 3, D) 4 and E) 5 in the embryonic ectoderm development (EED)
pocket. The H-bonds are depicted as green and red dash arrows, depending on
the behavior of the ligand as donor or acceptor, respectively. Conversely,
the main hydrophobic and aromatic interactions were depicted as yellow lines
and blue arrows, respectively.

Figure S6. 2D representation of the underlying
binding interactions of the hit compounds A) 1, B) 2, C) 3, D) 4 and E) 5 in
the SET pocket. The H-bonds are depicted as green and red dash arrows,
depending on the behavior of the

ligand as donor or
acceptor, respectively. Conversely, the main hydrophobic and aromatic
interactions were depicted as yellow lines and blue arrows, respectively.
Table S1. Protein
Data Bank (PDB) ID and Diffraction-component Precision Index (DPI) score for
both targets.
Table S2. Set of 250
actives compounds of SET.
Table S3. Set of 154
actives compounds of embryonic ectoderm development (EED).

Table S4. List of the shared hits, reported
their ADME-related parameters computed inside the Multi-Target Ligand
(Mu.Ta.Lig.) Chemotheca.

补充图S1：共结晶于胚胎外胚层发育蛋白（embryonic ectoderm development, EED）模型中的抑制剂(3R,4S)-1-[(2-甲氧基苯基)甲基]-N,N-二甲基-4-(1-甲基吲哚-3-基)吡咯烷-3-胺（LQD）的二维化学结构，其PDB编号为5U69。
补充图S2：EED结合口袋的药效团模型三维可视化结果。化学特征按颜色编码：黄色、绿色、红色球体分别代表疏水特征（HY）、氢键供体（HBD）与氢键受体（HBA）。
补充图S3：共结晶于SET模型中的S-腺苷-L-同型半胱氨酸（S-Adenosyl-L-Homocysteine, SAM）的二维化学结构，其PDB编号为5HYN。
补充图S4：SET结合口袋的药效团模型三维可视化结果。化学特征按颜色编码：黄色球体代表疏水特征（HY），绿色与红色箭头分别代表氢键供体（HBD）与氢键受体（HBA）。
补充图S5：命中化合物A)1、B)2、C)3、D)4及E)5在EED结合口袋中的潜在结合相互作用二维示意图。氢键以绿色与红色虚线箭头表示，分别对应配体作为供体与受体的场景；主要疏水与芳香相互作用则分别以黄色线条与蓝色箭头表示。
补充图S6：命中化合物A)1、B)2、C)3、D)4及E)5在SET结合口袋中的潜在结合相互作用二维示意图。氢键以绿色与红色虚线箭头表示，分别对应配体作为供体与受体的场景；主要疏水与芳香相互作用则分别以黄色线条与蓝色箭头表示。
补充表S1：两个靶点的蛋白质数据库（Protein Data Bank, PDB）编号与衍射组分精度指数（Diffraction-component Precision Index, DPI）得分。
补充表S2：SET靶点的250个活性化合物集合。
补充表S3：胚胎外胚层发育蛋白（EED）靶点的154个活性化合物集合。
补充表S4：共享命中化合物列表，附带其在多靶点配体（Multi-Target Ligand, Mu.Ta.Lig.）化学库中计算得到的ADME相关参数。