High-Throughput Screening

What high-throughput screening is

High-throughput screening (HTS) uses robots and automated lab tests to try very large numbers of compounds against a target or cell model, looking for ones that produce a measurable change. A 2011 review describes HTS as part of a proven scientific toolkit for discovering new chemical starting points, called chemotypes. [1] It is a search method. A compound that shows up in a screen is called a hit, and a hit is a starting point for more testing. This page is information only.

What a screen can show

A screen can show that a compound changed a signal in a specific test, such as the activity of a protein or the survival of cells in a dish. It can narrow thousands or millions of candidates to a short list worth studying. It tells you nothing yet about whether the effect happens in an animal or a person.

Why many hits are false leads

Some compounds appear active in many different screens, which makes them questionable starting points. A 2010 paper described chemical features that identify these "frequent hitters", called pan assay interference compounds (PAINS), which are promiscuous across many biochemical high-throughput screens. [2] The same paper warns that such compounds are increasingly common in the literature as potential starting points when they may not be. [2] For that reason a hit needs further testing before anyone treats it as meaningful.

From hit to medicine

Many promising medicines have failed to be safe and effective in human trials despite promising preclinical studies. [3] About 90 percent of clinical drug development fails. [4] Each step after a screen, including animal or human-cell tests and then Phase 1 to Phase 3 trials, exists because earlier results do not carry over. See the translational pipeline from laboratory to approval and clinical-trial phases explained.

What screening cannot establish

Where you may see "screening" claims

Wellness marketing sometimes says an ingredient "was screened against hundreds of targets". That describes an early lab method. It is not a human trial, and the correct label for it is preclinical. Treat any benefit claim based only on screening as a marketing claim. See mechanism vs demonstrated benefit.

Related methods

Computer modeling often selects which compounds to screen, see computational biology and molecular modeling. Screens can also be run on organ models, see organoids and organ-on-chip systems. AI approaches are covered in AI-assisted drug discovery.