Researchers map trends in drug development


One third of all approved drugs act on the same kind of important cell receptor – the G protein-coupled receptor, or GPCR. A comprehensive analyses of all GPCR-targeting drugs on the market and in clinical trials found that their pharmacological mechanisms are becoming more complex. The mapping also reveals rapid developments especially within Alzheimer’s disease, obesity, asthma and diabetes. This project was a joint collaboration between researchers at the University of Copenhagen, Denmark, and Uppsala University, Sweden.

From a drug perspective, GPCRs are the most utilised cell receptors in the body. They are uniquely accessible at the cell surface, and a third of all approved drugs achieve their therapeutic effect by interacting with cell surface GPCRs.

A new collaborative study by researchers at the University of Copenhagen and Uppsala University, of all drugs on the market and currently under development in clinical trials has been published in the prestigious journal Nature Reviews Drug Discovery. Researched mapped the molecular targets of all drugs that target GPCRs. This was performed for all approved drugs, as well as investigational drugs in clinical trials.

The mapping reveals trends for how these types of drug target a larger number or receptors and take advantage of new scientific principles to fine-tune their effects in order to achieve higher safety through more specific target interactions and cellular signalling.

“We can see the future trends when we compare the drugs on the market with those undergoing clinical trials. We can see, based on a number of parameters, that the new drugs targeting these receptors have more precise effects, are becoming more complex and have fewer side effects,” says Alexander Hauser, PhD student at the Department of Drug Design and Pharmacology.

Biological fine tuning

In recent years, researchers have learned more – largely through 3D atomic structures – about how G protein-coupled receptors are built and thus how they function. This knowledge appears to now have translated into drug development. The mapping shows that future drugs can be more specific, i.e. affect a fewer receptors, which results in fewer side effects.

There is also an increasing shift from small chemical drugs to more complex biological agents, and binding of drugs multiple sites on the receptor. The effects of these drugs can thereby be fine-tuned to become even more precise.

Focus on Alzheimer’s

The stringent collection of drug-target data has enabled the analyses of trends in the indication of GPCR-targeting drugs. The researchers were able to compare the number of drugs available on the market for a given disease with the number currently undergoing clinical trials.

“Several clinical trials are underway for Alzheimer’s and obesity, for which there have been very few effective drugs approved for the market. We also see many clinical trials related to asthma, diabetes and cancer. Far from all drugs undergoing clinical trials will end up becoming approved. But this mapping offers a good impression of where the focus is,” says David Gloriam.

The mapping also shows there is great potential for further research into these receptors. Over half the G protein-coupled receptors do not yet have a drug that targets them. There is therefore considerable untapped potential. Most of the untargeted receptors are related to genetic and immune system disorders.

The mapping was carried out under the leadership of Associate Professor David Gloriam and Alexander Hauser at the department of Drug Design and Pharmacology, in collaboration with Professor Helgi Schiöth and Misty Atwood at the department of Neuroscience, Uppsala University, and senior researcher Mathias Rask-Andersen at the department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.

Read the entire study: ‘Trends in GPCR drug discovery: new agents, targets and indications’

Fact box: G protein-coupled receptors

The GPCR superfamily comprises 800 receptor proteins on human cells. They sit in the cell membrane and relay signals from the outside into the cells.

Drugs can affect GPCRs in a multitude of ways. Essentially, when a substance binds to a receptor it can trigger a cascade of cellular signals. It can then forward a whole series of signals in the body.

One-third of all drugs approved by the US Food and Drug Administration (FDA) target this type of receptor in human cells.