Certain structural elements of a molecule can be responsible for toxicity. In fact, some substructural motifs occur more frequently in toxic compounds than in non-toxic ones. It therefore makes sense to eliminate such structural motifs from hits/leads as early as possible. Toxicity Checker is based on more than 100 toxic and promiscuous scaffolds. It displays an alert, when such a motif is found, and it displays the incriminated part of the molecule.
1. Go to LEAD OPTIMIZATION / TOXICITY CHECKER
2. Specify your existing hit/lead (either by drawing or by providing a chemical identifier such as mcule ID, SMILES, InChI or InChIKey)
3. Click on “CHECK”
4. If the compound contains any potential toxic substructure, “FAIL” message will be displayed along with your structure and the problematic motif in red
5. Go back and try to modify the problematic motif of your hit/lead
6. Click on “CHECK”
7. Continue the modifications, until no alert is displayed
8. You can use the other Lead Optimization tools, such as 1-Click Docking and Property Calculator to make sure other properties of the ligand are not impaired. In fact, try to improve multiple things simultaneously by checking all properties of the same idea.