# High-throughput screening and DNA-encoded libraries

Source: https://onco.cc/technologies/high-throughput-screening-libraries/  
OnCo record `high-throughput-screening-libraries` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Testing millions or billions of chemical compounds against a cancer target automatically to find starting points for new drugs.

## Summary

Robotic HTS of 1-2 million compound libraries, fragment screening by NMR or crystallography, DNA-encoded libraries (X-Chem, HitGen, WuXi; billions of compounds per pool), affinity-selection mass spectrometry, and virtual screening of ultra-large make-on-demand spaces (Enamine REAL, tens of billions) supply hits; CRISPR pooled screens (Broad DepMap, Sanger) supply the targets. Automation vendors: Beckman, Hamilton, Tecan, Thermo Fisher; readouts increasingly imaging-based (cell painting).

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-08
- Tags: supporting
- Principle: Parallel assays in microtitre plates or barcoded pools identify binders or phenotypic modulators, followed by hit confirmation and medicinal chemistry.
- Strengths: Unbiased hit discovery; DEL and virtual screening explore vast chemical space cheaply
- Limitations: False positives and assay artefacts; Hits far from drugs; Undruggable targets still resist

## Sources

- Goodnow et al., DNA-encoded chemistry: enabling the deeper sampling of chemical space (Nature Reviews Drug Discovery 2016): https://doi.org/10.1038/nrd.2016.213

## Connected records

- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/), [Ex vivo drug sensitivity screening in blood cancers (EXALT)](https://onco.cc/technologies/functional-precision-medicine-haematology/), [PROTACs & molecular glues (targeted protein degradation)](https://onco.cc/technologies/protac-degrader/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- companies: [Thermo Fisher Scientific](https://onco.cc/companies/thermo-fisher/)
- key papers: [Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without](https://onco.cc/key-papers/paper-depmap-tsherniak-cell-2017/), [DNA-encoded chemistry: enabling the deeper sampling of chemical space](https://onco.cc/key-papers/paper-goodnow-nat-rev-drug-discov/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/)

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