In several high-profile works, Virtual Screening using large enumerated ondemand libraries has repeatedly demonstrated its utility, in particular in earlier discovery stages. Seumer et al. used a genetic DND algorithm in conjuction with SAscore in the loop and synthesis planning post-processing to discover a novel organocatalyst . Grisoni and colleagues demonstrated successful syntheses by combining CLMs with a simplified retrosynthetic analysis based on a small number of robust reaction schemes geared towards lab on a chip technology . Merk and colleagues demonstrated several examples of using CLMs to prospectively design molecules for nuclear receptor targets (see also Fig. ) .