The University of North Carolina at Chapel Hill will pursue treatments for specific cancer targets as a specialized member of the National Cancer Institute’s renewed Experimental Therapeutics, or NExT, program through a contract with Leidos Biomed and its Frederick National Lab in Frederick, Maryland.
Because of its unique expertise, UNC has been designated a specialized center in the NCI’s Chemical Biology Consortium, the NExT program’s discovery engine. The university’s team is led by Stephen Frye, Ph.D., Fred Eshelman Distinguished Professor at the UNC Eshelman School of Pharmacy and director of the school’s Center for Integrative Chemical Biology and Drug Discovery. Frye is also a member of the UNC Lineberger Comprehensive Cancer Center and co-director of its molecular therapeutics program.
The pharmacy school’s CICBDD develops chemical “keys” that fit biological “locks” in the body. Usually these locks are proteins that start or stop processes that can be responsible for disease, and the keys are precursors to new medicines. When other researchers at UNC or in the NCI’s Chemical Biology Consortium find something that is an interesting lock to target in cancer, they can collaborate with the CICBDD to develop a small molecule key that might be useful as a drug.
The CICBDD’s most advanced project has been cleared by the FDA for Phase I clinical trials. It is a treatment for acute lymphoblastic leukemia and other cancers that inhibits a protein called mer kinase. The relationship between mer kinase and leukemia was uncovered by researchers in the lab of Shelley Earp, M.D., director of UNC Cancer Care and a member of UNC Lineberger. He brought the mer kinase target to Frye’s group so they could design inhibitors that could lead to a new class of cancer drugs.
The Frederick National Lab, sponsored by the National Cancer Institute, is managing the expansion of the Chemical Biology Consortium to 22 sites around the country with world-class expertise in high-throughput screening, structural biology, medicinal chemistry, compound profiling, cancer biology, and animal models for oncology. UNC will participate in the consortium via a research subcontract from Leidos Biomedical Research, Inc., prime contractor for the national lab.
In collaboration with the National Center for Advancing Translational Sciences, UNC is also close to optimizing a potential treatment for glioblastoma. The drug candidate targets mutant forms of IDH1, an enzyme that plays a role in the formation of the deadly brain tumors.
“The renewal of the CBC by NCI reflects a continuing commitment to collaborative translational research to advance cancer treatment,” Frye said. “UNC’s inclusion in the second generation of the CBC recognizes the value of our contributions and our potential to contribute to discovery of new therapies.”
NExT Steps
The NCI’s NExT Chemical Biology Consortium is a renewed and expanded collaborative network of 7 dedicated and 15 specialized centers supporting the advancement of early-stage drug-discovery projects through to the clinical candidate stage. Specialized centers like UNC are chosen for their uniquely focused technologies to advance projects at specific stages of discovery.
Within the UNC CICBDD, Frye has developed a multidisciplinary team of medicinal chemists, lead-discovery biologists and computational scientists, many with pharmaceutical industry experience, whose skills can readily applied to NExT projects.
As one of the 12 original members of the NCI consortium formed in 2009, UNC was awarded contracts for three cancer targets totally $8.9 million over six years that resulted in the potential treatments for leukemia and glioblastoma.
In addition to Frye, the consortium leadership at UNC includes Deputy Director and Fred Eshelman Distinguished Professor Jeffrey Aubé, Ph.D.; Director of Medicinal Chemistry Xiaodong Wang, Ph.D.; Director of Lead Discovery and Characterization Kenneth J. Pearce, Jr., Ph.D.; and Director of Computational Biophysics and Molecular Design Dmitri Kireev, Ph.D.
The CICBDD was established in 2007 with funding from the UNC Eshelman School of Pharmacy and UNC Lineberger with the mission of bringing dedicated medicinal chemistry and assay development expertise to bear on biological targets of therapeutic relevance under investigation by UNC faculty. The CICBDD receives ongoing annual support from the University Cancer Research Fund and received a generous gift from Fred Eshelman. The School was ranked number one among the nation’s pharmacy schools in U.S. News & World Report’s 2017 edition of American’s Best Graduate Schools.
UNC Lineberger is one of only 45 National Cancer Institute–designated comprehensive cancer centers and was recently rated exceptional – the highest category – by the National Cancer Institute. The University Cancer Research Fund was created in 2007 by the North Carolina General Assembly to provide ongoing state support for cancer research.