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

Abstract

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.

A Review on Emerging Trends and Technologies in Library

“…Creating a library game or gamifying certain elements of a library does not ensure that it will be well received by its intended audience. Games that are either too difficult or too boring are both poorly designed [30]. Naturally, designing and developing a good game is much more difficult than designing and developing a bad one.…”

DNA-Compatible Suzuki-Miyaura Cross-Coupling Reaction of Aryl Iodides With (Hetero)Aryl Boronic Acids for DNA-Encoded Libraries

“…During the past decade, the use of DEL technology provided a great opportunity to identify drug-like compounds that can bind selectively to a variety of target proteins ( Deng et al, 2012 ; Gentile et al, 2012 ; Disch et al, 2013 ; Samain et al, 2015 ; Seigal et al, 2015 ; Harris et al, 2016 ; Belyanskaya et al, 2017 ; Dawadi et al, 2020 ; Chamakuri et al, 2021 ). More recently, a number of different powerful applications leveraging the DEL technology have been proposed ( Huang et al, 2022 ; Sunkari et al, 2022 ; Zhao et al, 2022 ). To expand the chemical space of these DNA-Encoded Libraries, a greater variety of DNA-Compatible reactions is required.…”

Development of on-DNA vinyl sulfone synthesis for DNA-encoded chemical libraries

“…3 The conjugated DNA tags that could be read out by the sequencing technique enable the identification of those high-affinity binders within a complex pool, thus rendering high throughput screening (HTS) at a lower cost and efficient time (Scheme 1a). 4 This competitive strategy featuring unique DNA barcodes, thereby, has been harnessed by both the pharmaceutical industry 5 and academia, 6 to facilitate the early stage of drug discovery, undoubtfully generating fruitful outcomes of clinical candidates represented by the RIPK1 inhibitor GSK2982772, 7 sEH inhibitor GSK2256294, 8 and autotaxin inhibitor X-165, 9 which were optimized from the corresponding DEL hits.…”