Supplementary Information:

Decoys Preparation:

10 decoy molecules were prepared for each of 56 active Chk1 inhibitor (TP series) using Decoy finder tool. For decoy preparation, Maybridge screening collection database (http://www.maybridge.com/) was selected as source of decoys. Decoy finder tool provides flexible parameters for decoys preparation such as Tanimoto coeffcient between active ligand and decoy, H-bond donors, H-bond acceptors, molecular weight, rotatable bonds and logP. Parameters used for decoys generation are shown in Figure.S1.

Figure.S1. Parameters for decoys preparation (www.urvnutrigenomica-ctns.github.io/DecoyFinder).

Figure.S2. Docked conformation of HTS02185 (a) HTS08285 (b) HTS8286(c) and SPBO7479 (d) mapped to the pharmacophore model. For clear representation distance constraints are not shown.

Figure.S3. Combined view of docked conformation of all active hits mapped to pharmacophore model.

Known potent Chk1inhibitors
Hits / SCH900776[1] / LY2606368[2-3] / SAR-020106[4] / LY2606318[5-6] / Compound1[7]
HTS02185 / 0.175(FP2)
0.280(MACCS) / 0.242(FP2)
0.455(MACCS) / 0.252(FP2)
0.476(MACCS) / 0.297(FP2)
0.478(MACCS) / 0.174(FP2)
0.369(MACCS)
HTS08285 / 0.157(FP2)
0.340(MACCS) / 0.174(FP2)
0.359(MACCS) / 0.220(FP2)
0.439(MACCS) / 0.161(FP2)
0.365(MACCS) / 0.127(FP2)
0.386(MACCS)
HTS08286 / 0.184(FP2)
0.377(MACCS) / 0.210(FP2)
0.411(MACCS) / 0.221(FP2)
0.458(MACCS) / 0.207(FP2)
0.430(MACCS) / 0.157(FP2)
0.438(MACCS)
SPB07479 / 0.182(FP2)
0.329(MACCS) / 0.185(FP2)
0.321(MACCS) / 0.201(FP2)
0.370(MACCS) / 0.248(FP2)
0.395(MACCS) / 0.154(FP2)
0.352(MACCS)

Table. S1. Similarity analysis of active hits with few known Chk1 inhibitors in terms of Tanimoto coefficient.

References:

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