biostudies-literatureGhiandoni GMBiotechnology and Biological Sciences Research Councile2100207https://www.ebi.ac.uk/biostudies/studies/S-EPMC9285524biostudies-literatureUnknown41(4)Reaction-based de novo design refers to the generation of synthetically accessible molecules using transformation rules extracted from known reactions in the literature. In this context, we have previously described the extraction of reaction vectors from a reactions database and their coupling with a structure generation algorithm for the generation of novel molecules from a starting material. An issue when designing molecules from a starting material is the combinatorial explosion of possible product molecules that can be generated, especially for multistep syntheses. Here, we present the development of RENATE, a reaction-based de novo design tool, which is based on a pseudo-retrosynthetic fragmentation of a reference ligand and an inside-out approach to de novo design. The reference ligMolecular informaticsRENATE: A Pseudo-retrosynthetic Tool for Synthetically Accessible de novo Design.PMC9285524BB/R505821/11960252Hristozov DBodkin MJGillet VJWebster JGhiandoni GMWallace JEAChen BfalseRENATE: A Pseudo-retrosynthetic Tool for Synthetically Accessible de novo Design.Reaction-based de novo design refers to the generation of synthetically accessible molecules using transformation rules extracted from known reactions in the literature. In this context, we have previously described the extraction of reaction vectors from a reactions database and their coupling with a structure generation algorithm for the generation of novel molecules from a starting material. An issue when designing molecules from a starting material is the combinatorial explosion of possible product molecules that can be generated, especially for multistep syntheses. Here, we present the development of RENATE, a reaction-based de novo design tool, which is based on a pseudo-retrosynthetic fragmentation of a reference ligand and an inside-out approach to de novo design. The reference lig2022-01-01T00:00:00Z2022 Apr2025-04-18T22:59:31.876Z2025-04-07T10:41:23.02ZS-EPMC92855243475098910.1002/minf.202100207