CCSMD: A Database Built from Smart Reaction Modules and Combinatorial Chemistry and Used to Discover Anti-Cancer Small Molecules in Cancer Cell Lines

In drug development, the discovery of drugs with targeted properties often requires starting with the discovery of active lead compounds. The traditional process of discovering lead compounds is often costly, and virtual screening using large databases can be an emerging and promising approach. Here, a combinatorial chemical molecular database was created by virtual synthesis of many unexplored small molecule building blocks from public databases through the chemical reaction of amides, which was uploaded to the web for virtual screening of specific target protein CDK6 and actual synthesis of high fraction molecules, leading to the discovery of compounds 10 and 9 with IC50 values of 1.157 μM and 1.379 μM, validating the rationality and feasibility of the database. It was also verified that the amide reaction, the most widely used class of chemical reactions in drug synthesis, had an actual hit rate of 76.92% in this virtual combinatorial chemistry.