DIY Virtual Chemical Libraries - Novel Starting Points for Drug Discovery

The advancement of in silico technologies such as library enumeration and synthetic feasibility prediction has made drug discovery pipelines rely more and more on virtual libraries, which provide a significantly larger pool of compounds than in-stock supplier catalogs. Virtual libraries from external sources, however, may be associated with long delivery time and high cost. In this study, we present a Do-It-Yourself (DIY) combinatorial chemistry library containing over 14 million almost completely novel products built from 1000 low-cost building blocks based on robust reactions frequently applied at medicinal chemistry laboratories. The applicability of the DIY library for various drug discovery approaches is demonstrated by extensive physicochemical property, structural diversity profiling, and the generation of focused libraries. We found that internally built DIY chemical libraries present a viable alternative of external virtual catalogs by providing access to a large number of low-cost and quickly accessible potential chemical starting points for drug discovery.

Automated summary

In this study, a Do-It-Yourself (DIY) combinatorial chemistry library containing over 14 million almost completely novel products was presented. The library was built from 1000 low-cost building blocks and demonstrated its applicability in various drug discovery approaches. The internally built DIY chemical library was found to provide a viable alternative to external virtual catalogs by offering access to a large number of low-cost and quickly accessible potential chemical starting points for drug discovery.