A new database, ZINC-22, is freely available for access and download by everyone. The database contains over 37 billion enumerated, searchable, commercially available compounds in 2D, over 4.5 billion of which have been built in biologically relevant ready-to-dock 3D formats. The database can be searched online using whole molecule similarity, substructure, and patterns in 2D. The database includes molecules up to 29 heavy atoms (HAC29) and can easily be extended to HAC34 or higher. Over 95% of available molecules up to HAC24 have been built in 3D and over 80% of HAC25. We take up the features of the new database in turn. Because in stock compounds are important as an "informer set" that is often screened before a large-scale screen, ZINC-22 incorporates the ZINC20 informer set. The previous version of ZINC, ZINC20, continues to be maintained and contains all in-stock purchasable compounds, building blocks, and annotated compounds. From among the make-on-demand databases, ZINC20 only contains molecules that we had loaded prior to creating ZINC-22. (see Methods).