The University of North Carolina at Chapel Hill is the newest member of a pioneering international partnership that aims to completely map the single most successful targets for cancer drugs known to date and will share their work with no fees or restrictions on intellectual property. The unrestricted use of this map could lead to breakthrough medicines not only in the realm of cancer, but also for rheumatoid arthritis and a host of neurodegenerative disorders, including Parkinson's and Alzheimer's.
The partnership is known as the Structural Genomics Consortium, which began 11 years ago and includes Oxford University, the University of Toronto and the State University of Campinas in São Paulo, Brazil. UNC-Chapel Hill is the consortium's newest member and has launched the SGC-UNC on campus, thanks to startup funding from the UNC Eshelman Institute for Innovation, which was created by Fred Eshelman's gift to the pharmacy school in 2014.
"Because of Fred Eshelman's historic $100 million gift, we have been able to create the first SGC hub in the U.S.," said Chancellor Carol L. Folt. "SGC-UNC is going to help identify the best new targets for discovering breakthrough medicines, and we have Dr. Eshelman and an incredibly talented group of faculty, staff and students to thank for this remarkable effort."
UNC-Chapel Hill will focus on developing chemical tools that allow researchers to home in on the function of a family of proteins called kinases, enzymes that set in motion the machinery for cell growth and survival. They will then use these tools to create a functional map of this family, such that similar kinases would be grouped together. The map will help pharmaceutical companies, industry and academia narrow down on kinases they want to target for drug development depending on the disease they want to treat. Without the map, it is unclear which kinases are potential drug targets for any one disease.
"It's like exploring and opening up the American West," said Tim Willson, chief scientist of the Structural Genomics Consortium at UNC-Chapel Hill. "Everyone suspected there was something interesting out there, but until somebody went out there and made a map, people just didn't know where to build the railroads, or a new settlement. The pioneers had to go explore for the good of everyone and bring that knowledge back to share with everyone."
Although kinases have been one of the most productive areas of drug development, they are largely unexplored. Out of a family of approximately 500 proteins, only about 50 have been studied in depth, which has led to the creation of 26 drugs, 25 of which work to fight cancer - an overwhelming success rate for drug discovery. But despite their high-stakes therapeutic potential, more than 80 percent of kinases remain untapped due to the cost, risk and complexity of creating the chemical tools that yield such a map.
UNC has already seen success leveraging the SGC's work with protein kinases. In 2009, researchers at the UNC Lineberger Comprehensive Cancer Center identified a kinase that plays a role in various forms of cancer. At that time, the SGC, which did not include UNC-Chapel Hill, had already made the 3D structure of the kinase available to the public. Scientists then used the structure of the kinase to rapidly design and synthesize new compounds that shut down activity in human cancer cells.
Their work resulted in a spinoff company, Meryx, which was created in 2013 to develop new therapeutics based on the kinase inhibitors created at UNC-Chapel Hill.
"The UNC Eshelman School of Pharmacy knows firsthand the value of the work done by the SGC, and we are extremely proud to become a part of it," said Robert Blouin, dean of the school. "We are now at the center of a global network of activity that will generate many opportunities for drug discovery with protein kinases as targets for breakthrough medicines."
The new unit is made up of former employees of GlaxoSmithKline's Research Triangle Park location. GSK, one of the original funders of the SGC, is contributing the rights to use and distribute a library of chemicals developed and characterized by the company.
"The University of North Carolina at Chapel Hill is an outstanding institution, and their involvement in the SGC clearly signals their intent to speed the creation of new medicines for patients," said Aled Edwards, director and CEO of the Structural Genomics Consortium. "We're delighted to welcome UNC as our first site in the U.S."