SUMMARY: 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.

BACKGROUND: Acute oral toxicity of drug candidates can lead to drug development failure; thus, predicting the acute oral toxicity of small compounds is important for successful drug development. However, evaluation of the acute oral toxicity of small compounds considered in the early stages of drug discovery is limited because of cost and time. Here, we developed a computational framework, PredAOT, that predicts the acute oral toxicity of small compounds in mice and rats. METHODS: PredAOT is based on multiple random forest models for the accurate prediction of acute oral toxicity. A total of 6226 and 6238 compounds evaluated in mice and rats, respectively, were used to train the models. RESULTS: PredAOT has the advantage of predicting acute oral toxicity in mice and rats simultaneously, and its prediction performance is similar to or better than that of existing tools. CONCLUSION: PredAOT will be a useful tool for the quick and accurate prediction of the acute oral toxicity of small compounds in mice and rats during drug development.