Mcule offers a continuously growing set of intuitive, easy-to-use modeling applications specifically designed to evaluate and generate ideas in the hit/lead optimization process. In the course of a drug discovery project, after identifying a hit or lead molecule, the next step is the optimization of multiple properties of the hit/lead. Some of the properties that typically need further optimization are binding affinity to the target, selectivity (affinity to off-targets) and ADMET properties.
Molecular docking simulations predict the binding orientation and affinity of a ligand to a target. 1-Click Docking is the easiest molecular docking solution online. It has been designed to quickly test and rank-order ideas of medicinal chemists. Ideas can be prioritized based on the docking scores (predicted binding affinity) and interactions can be visualized between the ligand and the target.
Scaffold hopping is about finding novel active ligands structurally different from a reference ligand (Query). Scaffold hopping can be particularly useful during lead optimization, when certain parts of lead molecules need to be replaced to fix IP, toxicity, selectivity or pharmacokinetic issues. 1-Click Scaffold Hop utilizes the powerful FTrees Visual Similarities algorithm (link), which can identify structurally different scaffolds that are still active.
ADMET properties heavily depend on physicochemical properties. For example, high logP (> 5) and molecular weight (> 500 g/mol) are typically associated with unsuitable ADMET profile. Property calculator creates a physicochemical property profile for your compound in seconds. You can reject compounds with unsuitable logP, insufficient number of H-bond acceptors/donors, too many rotatable bonds, etc.
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.
Idea validator offers a fully customizable solution to validate and prioritize synthetic ideas. Business rules can be easily implemented. Feature set that can be integrated includes: activity prediction, target profiling, physicochemical property alerts, toxic alerts, commercial availability check