Assessing the scaffold diversity of screening libraries.
Medicinal chemists have traditionally realized assessments of chemical diversity and subsequent compound acquisition, although a recent study suggests that experts are usually inconsistent in reviewing large data sets. To analyze the scaffold diversity of commercially available screening collections, we have developed a general workflow aimed at (1) identifying druglike compounds, (2) clustering them by maximum common substructures (scaffolds), (3) measuring the scaffold diversity encoded by each screening collection independently of its size, and finally (4) merging all common substructures in a nonredundant scaffold library that can easily be browsed by structural and topological queries. Starting from 2.4 million compounds out of 12 commercial sources, four categories of libraries could be identified: large- and medium-sized combinatorial libraries (low scaffold diversity), diverse libraries (medium diversity, medium size), and highly diverse libraries (high diversity, low size). The chemical space covered by the scaffold library can be searched to prioritize scaffold-focused libraries.
CNRS UMR7175-LC1, Institut Gilbert Laustriat, 74 route du Rhin, F-67401 Illkirch Cédex, France.
Mireille
M
Krier
Guillaume
G
Bret
Didier
D
Rognan
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016000:Cluster Analysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D016208:Databases, Factual / Q000706:statistics & numerical data*; D018492:Dopamine Antagonists / Q000737:chemistry / Q000145:classification; D015394:Molecular Structure
D018492:Dopamine Antagonists