Finding the right molecule in a haystack of life–saving possibilities
Developing a new drug starts with identifying the molecule or “ligand” that can block the molecular target or “receptor” involved in a disease. Even with high throughput screening, finding that one functional ligand for a receptor from a haystack of millions of possible compounds is expensive, high–risk and time–consuming. Converting a promising target into a commercial drug typically takes about 15 years and costs up to $800 million.
To accelerate the discovery process, Canadian Glycomics Network (GlycoNet), in partnership with the Alberta Glycomics Centre (AGC) and the Derda Research Group at the University of Alberta (U of A), launched a service in January 2017 that enables academic scientists and biotech companies to identify that proverbial “needle” for a fraction of the time and cost. The 48Hour Discovery service can screen millions, even billions, of molecules simultaneously in a single test tube and get results in just 48 hours.
48Hour Discovery, one of four core services offered by GlycoNet, also offers opportunities for long–term partnerships with the AGC and GlycoNet’s network of world–leading researchers, government laboratories and industry partners.
“If it wasn’t for Alberta Glycomics Centre and GlycoNet, this would never have happened. They’ve been major contributors to funding research in this field,” says lead researcher Dr. Ratmir Derda.
To use the service, customers simply mail their target to Derda’s lab, and within two days, scientists will provide the molecular structure of hits/ligands and a prediction of how it will interact with the target.
“Companies or universities that want to do this on their own would normally have to spend millions of dollars on specialized infrastructure that can warehouse and process 100,000 to a million different compounds,” says Derda.
“The operating costs are also quite high,” he adds. “A typical molecular discovery process starts from testing a million different compounds to determine which one fits best with your target. At a typical cost of 50 cents per test per compound, the cost of even this simple, first step of discovery can be overwhelming. We significantly reduce the price for molecular discovery and simultaneously increase the number of accessible molecules by several orders of magnitude. We believe that accelerating the early drug discovery process will open new opportunities for drug discovery.”
Derda’s research team repurposed tools used in genomics – including next–generation sequencing, data mining and search management – and applied them to chemistry to analyze mixtures of millions of small ligands. A potential drug candidate, called a lead, is then used to “fish out” the right ligand. Identifying multiple high–quality leads remains a stubborn bottleneck in today’s drug discovery process.
“We work in the area of ligand receptor interaction, where the receptor is any kind of molecule – often a protein – that will uniquely bind to a target protein. It’s like finding the right key for the right lock that allows us to open it,” says Derda.
The in–house service leverages the research team’s expertise in molecular biology, informatics and biochemistry, as well as Canada’s decades of experience in glycomics and carbohydrates research. The project benefited from an early collaboration with Ferring Pharmaceuticals, whose expertise in phage display (a high through–put screening technique) and business acumen helped Derda develop a service that meets customers’ needs.
“If the length of time is too long and the process too high you give up on even trying to develop a drug for that particular target. It’s too much of a risk,” says Dr. John Dwyer, Senior Scientist, Protein Engineering at Ferring Pharmaceuticals, San Diego, California. “But with a service like this, it becomes cost–effective for a company to screen a wider array of compounds to identify something that works. Screening more targets and getting a drug to market much faster – that’s where I see the real advantages of this technology.”
Derda’s lab was Ferring’s first, and to date only research collaboration thus far in Canada. The company is currently working with the U of A team on new methods and new technologies to accelerate discovery in the rapidly growing global market for peptide drugs (peptides fall between the typical small molecule and larger biologics).
“Ratmir’s team is outstanding,” adds Dwyer. “When we’re looking for potential collaborators to help us, even some of the people I was interested in collaborating with would talk about how good Ratmir’s lab is. I soon realized I needed to talk to this guy.”
A new diagnostic tool
One of the first areas of healthcare likely to benefit from the 48Hour Discovery service is diagnostics. Derda says once a target has been identified, a simple diagnostic test for diseases like influenza and tuberculosis could be developed within months.
“Early diagnosis dramatically alters health care outcomes,” he says. “For some diseases, we might not even need better drugs; we just need to identify the disease earlier.”
Derda had another big reason for wanting to commercialize the 48Hour Discovery service. Unable to find good jobs in Alberta or Canada, many of his former graduates were moving to the U.S. and other countries. “I’m really hoping this service will grow over the next two to three years to become a self–sustaining company. It would give my students their first employment opportunity in a real industry and in Canada.”
For the original article, please visit: goo.gl/qovhR5