Researchers extensively reviewed drugs and agents in clinical trials that target G protein–coupled receptors on cells. This diverse array of drugs includes treatments for people with schizophrenia and popular weight-loss drugs. According to a researcher involved, the results can be used to repurpose existing drugs for new indications and to make designing new drugs less expensive and less risky.
Many drugs target G protein–coupled receptors. This category encompasses treatments across all therapeutic areas, but especially for people with obesity or diabetes and for people with schizophrenia, for example.
In 2017, a review article published in Nature Reviews Drug Discovery identified various drugs in this category and their specific cellular targets. The researchers have now updated this analysis, enabling drug developers to repurpose existing drugs for new indications and to create new drugs more cost-effectively.
“We reviewed what is available on the market and in clinical trials. This highlights gaps in drugs targeting specific G protein–coupled receptors and identifies opportunities to repurpose existing drugs for new indications,” explains a researcher behind the analysis, David Gloriam, Professor, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
An updated version of the analysis has now been published in Nature Reviews Drug Discovery.
Huge quantity of data
G protein–coupled receptors are a large class of proteins that reside in the cell membrane, with parts extending both inside and outside the cell. This unique structure enables these receptors to receive external signals and convert them into internal cellular responses.
These proteins are clearly highly relevant in pharmaceutics, since more than one third of all drugs have been developed specifically to target G protein–coupled receptors.
For their analysis, the researchers gathered extensive information about approved drugs and those undergoing clinical trials from databases of approved medicines, clinical trial databases, company websites, press releases, Google searches and other sources.
The data included details about the specific G protein–coupled receptor a drug binds to, the drug’s structure, its disease indication and additional relevant information.
Of 800 G protein–coupled receptors, about 300 can potentially be target proteins for drugs.
“Through this analysis, we identified trends in drug development. For instance, the number of drugs developed based on peptides, proteins and antibodies has notably increased, and the number of small-molecule drugs has decreased. However, small molecules still comprise as much as 71% of the drugs currently undergoing clinical trials,” says David Gloriam.
Weight-loss drugs target a G protein–coupled receptor
Several interesting numbers emerge from the results. For instance, 516 approved drugs worldwide target G protein–coupled receptors, 36% of all approved drugs.
These drugs include five of the top 50 best-selling drugs in 2023, including the fixed-dose combination of sacubitril and valsartan for treating people with heart failure.
The other three best-selling drugs that target G protein–coupled receptors are semaglutide, dulaglutide and tirzepatide, all of which are used for type 2 diabetes and obesity.
Many new drugs in the pipeline
Further analysis revealed that the 516 approved drugs target 121 G protein–coupled receptors, about one third of the G protein–coupled receptors that can be targeted with drugs.
There are 337 drugs currently being developed that target 133 G protein–coupled receptors, 30 of which are new targets for which no drugs have yet been developed.
Of the 337 drugs in clinical trials, 165 are drugs that have already received approval being studied for new indications, often referred to as old drugs for new diseases.
“Repurposing existing medicines for new indications presents less risk and is often more cost-effective than developing new medicines. Therefore, the fact that almost half of the drugs being studied in clinical trials are already approved for other indications is not surprising,” explains David Gloriam.
Drugs undergoing several clinical trials
The drug currently undergoing the most clinical trials is cannabidiol, which is being tested for 29 indications. Cannabidiol is approved for seizures associated with various diseases and is being investigated for autism, migraine and Parkinson’s disease.
Psilocybin, which has not yet been approved for any indication, is also being studied in numerous clinical trials for depression, post-traumatic stress disorder, obsessive-compulsive disorder and anorexia.
In addition, the results revealed that 23 G protein–coupled receptors are associated with specific diseases but have no existing drugs targeting them. Further, 27 G protein–coupled receptors are already targeted by drugs but not for all specific indications associated with the receptor.
These findings highlight the potential for developing new medicines to address many diseases.
Industry very interested
Based on their research, David Gloriam and colleagues have created a database that other scientists can explore to find new drug targets.
“We included a tool in the database for selecting drug targets. This tool enables drug developers to choose targets for their next project and determine what drugs exist for these targets, which diseases are indicated for these drugs and how various drugs bind structurally to the targets. The database makes identifying drug targets much easier and highlights relevant targets in a disease context for which no drugs have yet been developed,” says David Gloriam.
He elaborates that after the researchers completed the first version of the analysis in 2017, several drug developers approached them, seeking to hire them as consultants to help to identify new drug targets.
“I expect a similar response this time because interest in this area is significant,” concludes David Gloriam.
