High-power screening (HPS) empowered by DNA-encoded libraries

The world is totally dependent on medications. As science progresses, new, better, and cheaper drugs are needed more than ever. The pharmaceutical industry has been predominantly dependent on high-throughput screening (HTS) for the past three decades. Considering that the discovery rate has been relatively constant, can one hope for a much-needed sudden trend uptick? DNA-encoded libraries (DELs) and similar technologies, that have several orders of magnitude more screening power than HTS, and that we propose to group together under the umbrella term of high-power screening (HPS), are very well positioned to do exactly that. HPS also offers novel screening options such as parallel screening, ex vivo and in vivo screening, as well as a new path to druggable alternatives such as proteolysis targeting chimeras (PROTACs). Altogether, HPS unlocks novel powerful drug discovery avenues. We propose to group under the umbrella name HPS (high-power screening) technologies that screen an extremely large numbers [thousands to million times larger than HTS] (high-throuput screening) of chemical/biological compounds very effectively. The synergistic forces that differentiate HPS from HTS are the extra-large size of HPS libraries (combinatorial nature) and refinements for extremely efficient drug screening.HTS tests 1 million compounds in 1 million wells (50 000 compounds/week); HPS tests 1 billion compounds in a one tube (1 billion compounds/week).HPS offers novel screening options such as multiplex screening (parallel screening), thus allowing several screens to be performed at the same time (repeats, wild type vs mutants, different isoforms, competition with known compounds).Ex vivo screening is easily accessible with HPS.DNA-encoded libraries (DEL) technology offers new paths to druggable alternatives such as proteolysis targeting chimeras (PROTACs).