ZINC-22 is designed to scale in several ways. First, it allows tranches of chemical space to be built independently and asynchronously by colleagues who wish to contribute. This is achieved by compartmentalizing physical chemical space by heavy atom count and calculated logP. Second, the underlying design is a federation of databases, allowing it to be sharded across hundreds of computers; for instance, as of writing ZINC-22 is composed of 174 independent Postgres 12.0 databases, 110 Sn and 64 Sb (see Methods), and this can be easily scaled as the database grows. Third, the number of files used to store and distribute ZINC-22 has been reduced by packaging up to 5000 physically similar molecules together, reducing the strain on the filesystem.