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Drug Discovery Process More Accurate, Less Expensive Using Novel Mass Spectrometry Application

September 18, 2009

Cancer and cell biology experts at the University of Cincinnati (UC) have developed a new mass spectrometry-based tool they say provides more precise, cost-effective data collection for drug discovery efforts.

Preliminary studies have shown that the new totality spectrometry tool - known in the same proportion that MALDI-QqQMS (matrix-assisted laser desorption ionization-triple fourfold size spectrometer) - provides a more dignified substance of measuring the enzyme reactions critical to drug discovery at speeds worthy of comparison to currently available high-throughput screening systems at significantly depress costs.

“If introduced broadly, the recent generation mass spectrometry-based method we are proposing could significantly reduce the cost of running drug compound screening assays at the same time that too sparing remedy development teams substantial time by means of improving the accuracy of data collected,” explains Ken Greis, PhD, ally. professor and director of proteomics for the UC College of Medicine’s cancer and cell biology department.

Greis and his colleague Rakesh Rathore, PhD, give out their findings online ahead of print Sept. 17, 2009, in the scientific diary Rapid Communications in Mass Spectrometry.

In the drug discovery field, scientists employment the kind of is known in the same proportion that a “high-throughput screening system” to rapidly run thousands to millions of tests to screen for inhibitors of molecular targets that could be good in pharmaceutical drug development and in furthering of knowledge of the overall biological mechanisms in the rear a particular disease.

Typical assays for enzyme screening are fluorescence and chemiluminescence-based systems. To make those assays universal, vendors have developed standard kits using specialized - and costly - reagents to identify changes in the fluorescent or chemiluminescent signals.

“There are a couple of problems with the circulating approach: For starters, it’sitting any imperfect method that generates many false-positive “hits” and for exactly diligence, you be favored with to follow up on all inhibitors identified, what one. results in a lot of time and money wasted on false leads,” says Greis.

“Reagents are very costly repeatedly ranging betwixt 50 cents to $1 per sample. That adds up very immediately when you’re screening against a million-compound library,” adds Rathore, a postdoctoral fellow in Greis’ laboratory.

Greis and Rathore have developed a practice high-throughput screening method using a generalized platform. Unlike the commercially available systems that analyze byproducts and coupled reactions, their system directly measures and quantifies the substrate and the end produce of the recoil.

They say using mass spectrometry to measure the mass and quantity of the product gives researchers a dispose measure of the assay and more trustworthy compounds to scrutinize, eliminating the chances for molecular interference common with chemiluminescence and fluorescence-based systems.

“Analytically, our mass spectrometry-based application provides superior premises and in addition eliminates the issue of producing northerly numbers of false results, saving a tremendous amount of time chasing from a thin to a dense state bad leads on unsalable article targets. And on this account that we are using these non-tagged reagents, it no other than costs us 3 to 5 cents per pattern to run these assays, which is a very large require to be paid savings,” adds Greis. “That can contemplate the schism between $50,000 and $1 the great body of the people in reagent costs for a single screening project.”

The approach developed by the UC group also holds appeal in that it has multiplexing capabilities - making it in posse to, measure inhibitors for sum of two units or more enzymes with one live through through the compound repository. Typical assays start with one mark enzyme and that is tested against an entire compound repository to look for inhibitors. Once inhibitors are identified, researchers must then follow up on each one to know if it has any validity as a drug target.

“Now instead of doing a million-dollar campaign that takes a month to run and then another million-dollar campaign that takes another month to run, we can do the pair at the same time while still avoiding the false-positives and false-negatives usual through popularly available methods,” says Greis. “This is the same of those disruptive technologies that could completely change the regular course people do this type of screening work.”

The UC team is working on identifying funding to transition this mass spectrometry-based technology into a fully automated system for relating to traffic use.

In addition to Greis and Rathore, coauthors of the study take in William Siebel, PhD, of UC’s Drug Discovery Center and Jay Corr, PhD and Daniel Lebre, PhD, of MDS Analytical Technologies. Rathore’sitting fellowship is funded by MDS Analytical Technologies.

Source:
Amanda Harper
University of Cincinnati Academic Health Center

Written by Samanta · Filed Under Pharmacy Industry News