3D-Diversity Natural-Product-Like Library

ChemDiv’s 3D-Diversity Natural-Product-Like Library contains 21,000 compounds.

Natural products (NP) have been widely used for the treatment of diseases and illnesses for many years. Analysis of NPs over the past 30 years revealed that approximately 40% of the developed therapeutics drugs approved by FDA were NPs, NP derivatives, or synthetic mimetics related to NPs. With their highly and sophisticated biological and chemical diversity, NPs and their derivatives have been used to explore biologically relevant space. The significant impact of NPs on the discovery of therapeutic agents is based on their embedded biosynthetic molecular recognition. [1]

3D diversity is pivotal because the molecular shape is one of the most important factors in molecular recognition by a biomolecule. The library contains 1479 clusters based on the pharmacophore 3D-similarity metric and 738 unique heterocycles. The key concepts that underlie the library design are 3D shape, pharmacophore diversity, drug-likeness, and chemical beauty. 3D library advantages over 2D ones are in higher sp3 and QED values. The compound selection pipeline consists of four stages to select the most diverse and active molecules from each cluster.

[1]         M. Pascolutti and R. J. Quinn, “Natural products as lead structures: Chemical transformations to create lead-like libraries,” Drug Discovery Today, vol. 19, no. 3. Elsevier Ltd, pp. 215–221, Mar. 01, 2014, doi: 10.1016/j.drudis.2013.10.013.