Scaffold‐Based Libraries Versus Make‐on‐Demand Space: A Comparative Assessment of Chemical Content

Le résumé fourni par la source

Chemical libraries are essential in drug discovery, providing a vast variety of compounds for screening and exploration. Previously, through collective efforts of chemoinformaticians and chemists, the group has created two libraries: the essential eIMS containing 578 in-stock compounds on plates ready for high throughput screening and a companion virtual library vIMS, containing 821.069 compounds derived from the scaffolds of the eIMS compounds, and decorated with substituents from customized collection of R-groups. In this article, validation of this library design approach is aimed, which is built on scaffold-based structuring and decoration guided by chemists' expertise. Specifically, its effectiveness is evaluated in comparison to the widely adopted reaction- and building block-based approach. Using Enamine REAL Space library, two scaffold-focused datasets are developed and the make-on-demand chemical space containing the same scaffolds are systematically compared. The results showed similarity between the two, but with limited strict overlap. Interestingly, a significant portion of the R-groups are not identified as such in the make-on-demand library. Synthetic accessibility analysis of the compound sets indicated overall low to moderate synthetic difficulty. These findings confirm the value of the scaffold-based method for generating focused libraries, offering high potential for lead optimization in drug discovery.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.