By contrast, commercially available virtual, synthesis-on-demand chemical catalogs offer compounds with high synthetic success rates and quick turn-around. These catalogs continue to grow rapidly, roughly doubling in size every six months (Figure ). Their growth is spurred largely by advances in combinatorial chemistry, in which chemical building blocks are transformed into synthons with experimentally validated reactivity features ensuring high synthetic success rates and rapid synthesis . Importantly, a recent evaluation of several Combinatorial Synthesis Libraries (CSLs) found that more than half of all FDA approved drugs had an analog in the library with maximum common substructure (MCS) similarity exceeding 0.82 . The close similarity to approved drugs means those analogs likely share biologically active scaffolds and exhibit comparable physicochemical properties and toxicological safety profile. These results suggest that CSLs can provide significant value throughout pre-clinical drug discovery and development pipelines, beyond hit discovery into hit-to-lead and lead optimization.