Pharmaceutical companies amass huge libraries of chemical compounds they can test to see if one just might be capable of being developed into a new drug. But what if, even with millions of compounds, you’re missing some that could lead to your next blockbuster treatment?
That was the idea behind Friday’s announcement that AstraZeneca and Sanofi will swap 210,000 compounds from their libraries, giving each company new compounds to screen. (It’s worth noting, as STAT Pharmalot Ed Silverman columnist points out, “the move comes as both companies struggle to replenish their product portfolios and appease restive shareholders.”)
Companies measure the potential of the compounds through a process called high-throughput screening, in which the compounds are tested on different cells or molecules to see if they are a “hit” for a certain disease target. If there is a hit, scientists work to refine the compound and then start testing it in animal models to explore if it could eventually provide the foundation for a new drug. It takes years even if all goes well, but it’s one key way that drugs are discovered. (Companies also try to design compounds specifically for certain disease targets instead of doing the mass testing that this type of screening requires.)
Here are six things you should know about compound libraries, and how different groups are trying to leverage them to improve drug discovery.
The companies don’t worry about honing in on the same compound
Companies want to protect their compounds: They spend a lot of money building and acquiring new ones, and they are intellectual property. So what if a compound turns out to be a hit for both Sanofi and AstraZeneca? First off, most hits don’t actually lead to new drugs. And even if both companies pursued the same chemicals, their scientists do so much work creating “lead compounds” and improving them that any resulting drugs would almost certainly not match. “Each of those is just a potential starting point for a drug discovery project,” said Stephen Frye, a former GlaxoSmithKline scientist who now directs the Center for Integrative Chemical Biology and Drug Discovery at the University of North Carolina at Chapel Hill. That’s why the trade between the two companies involves what is known as “precompetitive” research.
AstraZeneca has shared before with industry
About four years ago, AstraZeneca and Bayer opened up their libraries to each other, but they only screened the compounds on targets that were not relevant to the other company. (In the AstraZeneca-Sanofi deal, no restrictions were placed on the screening.) One interesting discovery: Scientists from AstraZeneca and Bayer reported in Drug Discovery Today in 2012 that there was little overlap between the two collections, concluding that “one can effectively access a large collection of additional, diverse, high-quality and well-kept screening compounds … [in] the screening collection of a competing pharmaceutical company.”
…and with academia
Last year, AstraZeneca launched a partnership with the Academic Drug Discovery Consortium, a network of more than 130 academic drug discovery centers formed in 2012. The consortium does not have its own compound library, and academic institutions may only have a few thousand compounds in their libraries. With the partnership, selected researchers get access to 250,000 of AstraZeneca’s compounds. The compounds are sent to the scientists, who perform the screening on targets they develop. For researchers, the program opens the door to a wealth of compounds, and for AstraZeneca, the company typically gets the first chance to license any promising technology. “A lot of the biology expertise and knowledge about the genes and the disease, that comes largely from academia,” said Matthew Hartman, secretary and treasurer of the consortium.
Biotech and pharma will partner with the government as well
Robots at the National Center for Advancing Translational Sciences, an arm of the National Institutes of Health, perform 3 million tests a week of roughly 500,000 compounds on different disease targets. The scientists there regularly work with biotechnology companies who want to study how certain disease targets respond to certain compounds. “They may not have the chemical libraries, they may not have the screening technology,” said Ajit Jadhav of NCATS. The center’s researchers can also help the companies polish the compounds to get them ready for further testing.
Europe’s in the game
Scientists recently formed the Joint European Compound Library with 321,000 compounds that originated in pharmaceutical companies’ libraries and plan to make 200,000 more compounds in the next four years. The library will be open to academics and biotech companies who otherwise would not have access to such a collection. “The emerging picture of a low chemical similarity between the independent screening libraries suggests that an efficient and cost-effective way to generate a highly diverse library would be to combine the libraries from multiple companies,” scientists wrote in February in Drug Discovery Today. “The combined chemical space explored by all the collections would be available and this would maximize the chances of hits against a novel biological target.”
Some pharmaceutical companies are sharing selections, but don’t expect open access
The compounds remain incredibly valuable to companies. “The library, the chemical compounds, are usually the cherished jewel of the company,” said Barbara Slusher, president of the Academic Drug Discovery Consortium and neuroscientist at Johns Hopkins University. “So they’re still quite reluctant to give that out in an unencumbered fashion.”