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.The drug discovery process: present and future Scientific progress and novel technologies are helping to uncover disease causes faster than ever before. Novel emergencies such as the advent of new pathogens (e.g., SARS-CoV2) are further pressuring the pharmaceutical world. To be even faster, cheaper, and more accessible to academia, a new type of power is urgently needed.

An efficient method for the C-C bond formation via water soluble Na2PdCl4/sSPhos mediated Suzuki-Miyaura cross-coupling reaction of DNA-conjugated aryl iodide with (het)aryl boronic acids has been developed. This reaction proceeds at 37°C in water and acetonitrile (4:1) system. We also demonstrated that numerous aromatic and heteroaromatic boronic acids of different electronic natures, and harboring various functional groups, were highly compatible providing the desired coupling products in good to excellent yields. This DNA-compatible Suzuki-Miyaura cross-coupling reaction has strong potential to construct DNA-Encoded Libraries (DELs) in the context of drug discovery.

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