sorry, we can't preview this file

...but you can still download Supplementary materials _rev.docx
Supplementary materials _rev.docx (1.24 MB)

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

Download (1.24 MB)
dataset
posted on 29.03.2022, 10:30 by Roberta Rocca, Raffaella Catalano, Annalisa Maruca, Pierfrancesco Tassone, GIULIA PANZARELLA, Giosuè Costa, Francesco Ortuso, Stefano Alcaro

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.

Funding

Associazione Italiana per la Ricerca sul Cancro 21588 Ministero dell'Istruzione, dell'Università e della Ricerca x 201744BN5T

History