The discovery is bound to send shockwaves throughout the industry as it could lead to the production of currently available medications that are much more powerful.
Researchers believe they have found a way to change the action of 60 per cent of current treatments for diseases including heart disease, cancer, diabetes, depression and arthritis. The study describes a new way to manipulate one of the most important signalling mechanisms in human cells: G-protein coupled receptors (GPCRs).
GCPRs are targeted by 12 of the top 20 selling drugs, including Coreg for congestive heart failure, Cozaar for high blood pressure, Zoladex for breast cancer, Buspar for anxiety and Clozaril for schizophrenia, as well as by Zantac and Claritin. Together the drug class accounts for $200bn (€159 bn) in annual sales.
"We believe we have discovered a new class of drugs that could make current drugs more effective, but that also represents a completely new, independent way of treating the same diseases," said Alan Smrcka, associate professor of Pharmacology, Physiology, Oncology, Biochemistry and Biophysics at the >University of Rochester Medical Center.
"Early, pre-clinical experiments, for example, have found that one of our compounds could make morphine 11 times more potent," said Smrcka, who is also the article's lead author.
Scientists believe they have found a new way to regulate the same GCPR pathways, but at different points. Where most drugs change the behaviour of GPCRs on the outside of cells, the new class of drugs seeks to influence related signalling on the inside.
Since 1994 the existence of one location on the beta-gamma subunit of the G protein, which researchers called a "hotspot," has given them hope as they discovered the majority of the subunit's interactions with enzymes take place here.
Such a hotspot would represent a crucial new target for anyone trying to manipulate the G protein subunit to fight disease.
Smrcka's team performed an experiment to see which drug-like molecules from an existing database of 1990 known structures would bind tightly to the hotspot, and to rank them.
In general, tight binding suggests that a drug candidate has the potential to remain bound to its target long enough to have the desired effect. Of the compounds found through the screen, one, called M119, had a high enough affinity for the hotspot to be chosen as a lead compound in further experiments.
In a standard drug discovery technique, researchers collected several compounds (21 in this case) similar to their lead compound to see if any small change to the lead would drastically affect its drug potential.
Researchers tested two compounds, M119 and M201, which bound most effectively to the hotspot, on two biological systems that the G protein gamma-beta subunit controls. In one, white blood cells home in on the site of infection. The other involves morphine pain relief.
In white blood cells, the free G protein gamma-beta subunit activates enzymes that allow the cells to home in on the site of infection. Researchers found that M119 reduced activation of enzymes that encourage inflammation.
While M119 did block the action of an enzyme involved in inflammation (PI3kinase), it did not block related signals necessary for basic cell function.
"Imagine if we could identify 50 small molecules, with each one bringing about a specific set of changes in the behaviour the hotspot," Smrcka said.
"Taken together, this arsenal would grant us precise control over one of the most important biochemical switches in the body. This area of study is so important because of the sheer number of drugs already on the market that could be made more effective by differential targeting."
Many current, best-selling drugs work by binding to G-protein-coupled transmembrane receptors in the place of ligands on the outside of cells. A successful drug will either shut down or turn up the function of the GPCR as compared to its natural binding partner, whatever is called for to solve the problem.