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High Content Screening in Neurodegenerative Diseases

High Content Screening in Neurodegenerative Diseases

Published on: January 6, 2012

Origin and evolution of high throughput screening.

D A Pereira¹, J A Williams

¹Exploratory Medicinal Sciences, Pfizer Global R&D, Eastern Point Road, Groton, CT 6340, USA.

British Journal of Pharmacology

|July 3, 2007

Summary

High throughput screening (HTS) in drug discovery evolved from natural products to synthetic compounds, significantly increasing screening capacity and integrating ADMET targets. This advancement accelerated the identification of drug candidates, becoming crucial for pharmaceutical portfolios.

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Area of Science:

Pharmacology
Drug Discovery
Biotechnology

Background:

The article traces the historical development of high throughput screening (HTS) within a pharmaceutical company (Pfizer, Groton, USA).
HTS originated from natural product screening in 1986, transitioning to synthetic compounds using 96-well plates and micro-liter assay volumes.

Observation:

Initial HTS efforts screened 800 compounds weekly, scaling to 7200 by 1989 with centralized operations for efficiency.
Technological advancements included autoradiography, image analysis, and multiplexed assays (RT-PCR) for target identification.
By 1992, HTS contributed starting material for 40% of the drug discovery portfolio.

Findings:

HTS methodology expanded to include Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) targets by 1995.
Automated high throughput liquid chromatography-mass spectrometry (LC-MS) was developed for ADME target detection.
By 1999, ADME HTS was fully integrated into the drug discovery cycle, with adapted assays like the Ames test and micronucleus assay.

Implications:

The evolution of HTS significantly enhanced the early stages of drug discovery, increasing efficiency and scope.
Integration of ADMET screening early in the process improves the quality and success rate of drug candidates.
This historical perspective provides insights into the practical challenges and innovations in establishing HTS capabilities in the pharmaceutical industry.