Drugs and Drug-Like Compounds: Discriminating Approved Pharmaceuticals from Screening-Library Compounds

摘要

Compounds in drug screening-libraries should resemble pharmaceu-ticals. To operationally test this, we analysed the compounds in terms of known drug-like filters and developed a novel machine learning method to discriminate approved Pharmaceuticals from "drug-like" compounds. This method uses both structural features and molecular properties for discrimination. The method has an estimated accuracy of 91% in discriminating between the Maybridge Hit-Finder library and approved Pharmaceuticals, and 99% between the NATDi-verse collection (from Analyticon Discovery) and approved Pharmaceuticals. These results show that Lipinski's Rule of 5 for oral absorption is not sufficient to describe "drug-likeness" and be the main basis of screening-library design.