New drug discoveries are closely linked to the quality of lab procedures

July 21, 2020

In their quest to find new drugs to treat deadly diseases, scientists study millions of molecules at high speed at the same time. Often it is enzymes that are investigated as targets in these 'high-throughput' screenings.

New research from the University of Bath in the UK suggests the quality of the lab procedure (or assay) used for these screenings (measured by the "Z' value") has a much bigger impact on the ability to identify effective new molecules than was previously thought. The Z'-factor - which can never be greater than 1.0 - is a statistical measure of the researchers' ability to see the required signal. It is used to judge whether the response in a particular assay is large enough to warrant further attention.

As a result of the new study, pharmaceutical companies and other labs around the world will be under pressure to refine their techniques for investigating new drug candidates.

In recent years, there has been an explosion of studies involving enzymes. These studies aim to identify molecules that can be developed into new drugs for treating cancers, infectious diseases and neurodegenerative diseases, amongst other conditions.

"There are a lot of diseases out there for which there is no treatment or the treatments aren't very good," said Dr Matthew Lloyd, who led the study from the University's Department of Pharmacy and Pharmacology. "This explains why there is such a big drive to develop new treatments using high-throughput screening."

In a paper published this month in the Journal of Medicinal Chemistry, Dr Lloyd identifies 75 examples of 'hit' molecules that went on to the next stage of early drug discovery. This is the first time high-throughput screening involving enzymes has been subject to such a focused review and analysis. Dr Lloyd examined scientific papers published between 2002 and 2020 and found that hit frequency was closely linked to assay quality, as measured by the Z'-factor.

Dr Lloyd found that a Z'-factor of 0.65 had an average hit rate of 0.22% whereas a Z'-factor of 0.8 had an average hit rate of 0.83%, clearly demonstrating the significance of an optimised assay.

"These findings underline how important it is to make sure your assay is the best possible quality it can be," said Dr Lloyd. "A high Z' factor, indicative of high-quality lab procedures, enables more hits to be found and ultimately should increase the chances of new treatments being developed.

"Some studies are currently using assays that are not very good in terms of the Z'-factor. It was thought that 0.5 was acceptable but this review shows a level between 0.75 and 0.8 is the minimum that should be aimed for.

He added: "I suspect some researchers don't realise there is such a pronounced effect, which is why they settle for assay with a Z' of 0.7. But in the future, people in industry will need to be mindful of the results of my analysis when they are
-end-
Notes

To arrange interviews with Dr Lloyd, please contact Vittoria D'Alessio in the University of Bath press office via vda26@bath.ac.uk or call 01225-386319.

The University of Bath

The University of Bath is one of the UK's leading universities both in terms of research and our reputation for excellence in teaching, learning and graduate prospects.

The University is rated Gold in the Teaching Excellence Framework (TEF), the Government's assessment of teaching quality in universities, meaning its teaching is of the highest quality in the UK. In the Research Excellence Framework (REF) 2014 research assessment 87 per cent of our research was defined as 'world-leading' or 'internationally excellent'. From developing fuel-efficient cars of the future, to identifying infectious diseases more quickly, or working to improve the lives of female farmers in West Africa, research from Bath is making a difference around the world.

Find out more: http://www.bath.ac.uk/research/

Well established as a nurturing environment for enterprising minds, Bath is ranked highly in all national league tables. We are ranked 6th in the UK by The Guardian University Guide 2020, 5th for graduate employment in The Times & Sunday Times Good University Guide 2019, and 9th out of 131 UK universities in the Complete University Guide 2021.

University of Bath

Related Enzymes Articles from Brightsurf:

Bacilli and their enzymes show prospects for several applications
This publication is devoted to the des­cription of different microbial enzymes with prospects for practical application.

Ancient enzymes can contribute to greener chemistry
A research team at Uppsala University has resurrected several billion-year-old enzymes and reprogrammed them to catalyse completely different chemical reactions than their modern versions can manage.

Advances in the production of minor ginsenosides using microorganisms and their enzymes
Advances in the Production of Minor Ginsenosides Using Microorganisms and Their Enzymes - BIO Integration https://bio-integration.org/wp-content/uploads/2020/05/bioi20200007.pdf Announcing a new article publication for BIO Integration journal.

Cold-adapted enzymes can transform at room temperature
Enzymes from cold-loving organisms that live at low temperatures, close to the freezing point of water, display highly distinctive properties.

How enzymes build sugar trees
Researchers have used cryo-electron microscopy to elucidate for the first time the structure and function of a very small enzyme embedded in cell membranes.

Energized by enzymes -- nature's catalysts
Scientists at Pacific Northwest National Laboratory are using a custom virtual reality app to design an artificial enzyme that converts carbon dioxide to formate, a kind of fuel.

Mathematical model reveals behavior of cellular enzymes
Mathematical modeling helps researchers to understand how enzymes in the body work to ensure normal functioning.

While promoting diseases like cancer, these enzymes also cannibalize each other
In diseases like cancer, atherosclerosis, and sickle cell anemia, cathepsins promote their propagation.

Researchers finally grasp the work week of enzymes
Scientists have found a novel way of monitoring individual enzymes as they chomp through fat.

How oxygen destroys the core of important enzymes
Certain enzymes, such as hydrogen-producing hydrogenases, are unstable in the presence of oxygen.

Read More: Enzymes News and Enzymes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.