The Synthetically Accessible Virtual Inventory (SAVI) project aims at computationally generating a very large number of easily and inexpensively synthesizable novel screening compounds for the purpose of drug discovery. In SAVI, products are not generated by just applying SMARTS transform patterns to building block structures of unknown availability. We instead combine a set of transforms richly annotated with chemical context, coming from, or being newly developed in the mold of, the original LHASA project knowledgebase, with a set of highly annotated, reliably available, purchasable starting materials. These are reacted together <i>in silico </i>with custom scripts and capabilities in the chemoinformatics toolkit CACTVS. Each product is annotated with a number of computed properties seen as important in current drug design, including rules for identifying potentially reactive or promiscuous compounds. After having produced and made publicly available the first (beta) set of 283 million SAVI products annotated with proposed one-step syntheses, we are here reporting on the second full production run aimed at creating a database of more than one billion high-quality, easily synthesizable screening samples using approximately 1 million building blocks and more than 50 transforms, including modern popular chemistry such as Suzuki coupling and Buchwald-Hartwig reaction etc. We will present an analysis of the thus generated molecules, as to properties such as structural diversity, novel rings formed, and drug-likeness. We will report on the current status, ongoing developments, as well as scientific and technical challenges of the project.

Analysis of billions of Synthetically Accessible Virtual Inventory (SAVI) compounds as to their drug potential

2019 Spring National Meeting

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