MOESM1 of Identifying new topoisomerase II poison scaffolds by combining publicly available toxicity data and 2D/3D-based virtual screening
Creators: name: Lovrics, Anna
name: Pape, Veronika
name: Szisz, Dániel
name: Kalászi, Adrián
name: Heffeter, Petra
name: Magyar, Csaba
name: Szakács, Gergely
Publisher: name: figshare
Year: 2019
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cancer
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Computational Biology

description: Additional file 1: Additional text. Additional Text includes the commands used for the ROCS (OpenEye Scientific Software, Santa Fe, NM) and CFP (ChemAxon Ltd., Budapest, Hungary) similarity calculations and Additional Figures and Tables. Figure S1. Flowchart depicting the selection and comparison of DTP molecules used in this study. Figure S2. Histogram of pairwise Pearson correlation values among NSC duplicates (a) and desalted structure duplicates (b). Dashed vertical red line represents the Pearson correlation threshold used in this study to select scaffold-hopping analogues of mitoxantrone, while continuous red vertical line represents the cut-off for keeping duplicate structures. Figure S3. Distribution of the 11,797,653 pairwise similarity values supplemented with the bootstrapped distributions (continuous lines), where available. The vertical lines show the 95% confidence intervals of the bootstrapped distributions. Figure S4. Additional scaffold hopping candicates of either mitoxantrone, ametantrone, amsacrine or etoposide. Cf. Fig 3 in main text. Figure S5. Example gel photos displaying dose-response Top2 poisoning of NSC637992 and mitoxantrone. Dose response curves were calculated based on the intensities corresponding to the decatenated DNA (red arrow). Figure S6. Scaled density of the docking scores calculated for candidate scaffold hopping analogues of mitoxantrone (blue), the ‘3D decoy’ and the ‘biological decoy’ sets (orange and red, respectively) and the DUDE-E decoys (grey) when the similarity threshold values were chosen as the strictest (a) and most lenient (b). Figure S7. NSC660839, the ‘3D decoy’ molecule tested in the in vitro decatenation assay. Figure S8. Known Top1 inhibitor scaffolds: camptothecins (NSC94600), indenoisoquinolines (NSC314622), indolocarbazoles. Figure S9. Scaffold hopping candidates of camptothecin obtained using threshold values BA &gt; 0.49, ROCS &gt; 0.51, CFP ≤ 0.34. Figure S10. NSC24818 (podofilox). Figure S11. Scaffold hopping candidates of NSC24818 obtained using threshold values BA &gt; 0.41, ROCS &gt; 0.48, CFP ≤ 0.30. Table S1. Pearson correlation (BiolAct similarity) of the pIC50 values of annotated Top2 poisons to mitoxantrone. Table S2. Selected similarity thresholds to identify putative scaffold hopping analogues of mitoxantrone. Table S3. Docking scores and rankings (from 1173 compounds) of mitoxantrone and its scaffold hopping candidates. Table S4. Maximum of biological, ROCS and 2D similarities compared to mitoxantrone, ametantrone, amsacrine or etoposide. Additionally, docking scores of these compounds. Table S5. Similarities compared to published Top2 ligands and docking scores of 3D decoy agents. Table S6. Similarities compared to published Top2 ligands and docking scores of biological activity decoy agents. Table S7. Docking scores of DUDE-E decoys.