ChemBounce: a computational framework for scaffold hopping in drug discovery

Abstract

Scaffold hopping is a critical strategy in medicinal chemistry for generating novel and patentable drug candidates. Here, we present ChemBounce, a computational framework designed to facilitate scaffold hopping by generating structurally diverse scaffolds with high synthetic accessibility. Given a user-supplied molecule in SMILES format, ChemBounce identifies the core scaffolds and replaces them using a curated in-house library of over 3 million fragments derived from the ChEMBL database. The generated compounds are evaluated based on Tanimoto and electron shape similarities to ensure retention of pharmacophores and potential biological activity. By enabling systematic exploration of unexplored chemical space, ChemBounce represents a valuable tool for hit expansion and lead optimization in modern drug discovery.Availability and implementation The source code for ChemBounce is available at https://github.com/jyryu3161/chembounce. In addition, a cloud-based implementation of ChemBounce is available as a Google Colaboratory notebook.