Cancer center researcher awarded U.S. patent for possible applications in cancers

An innovation by IU Simon Comprehensive Cancer Center researcher Tao Lu, Ph.D., was awarded a patent by the United States Patent and Trademark Office. The patent was given on June 15 for “Small Molecule Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor and Methods of Treatment.”

Lu is a full member of the Experimental and Developmental Therapeutics (EDT) program at the cancer center and associate professor of pharmacology and toxicology and a Showalter Scholar at IU School of Medicine.

This innovation has opened a new avenue for the development of a novel class of drugs targeting hyperactive PRMT5 in different diseases, such as gastrointestinal (GI), breast and blood cancers. Lu made the discovery with Lakshmi Prabhu, Ph.D., a former doctoral student in her lab. The IU Innovation & Commercialization Office (ICO), especially Senior Technology Commercialization Manager Lakshmi Sastry-Dent, Ph.D., assisted with the patent application, according to Lu.

“PRMT5 is currently a hot therapeutic target pursued by several big pharmaceutical companies, affirming the cutting-edge nature of this patent and research,” Lu said. “Our research group has discovered a novel compound that possesses a unique structure and has proven to be one of the best in the class of PRMT5 inhibitors.”

The initial discovery of PRMT5 as a novel therapeutic target was made by Lu’s research team years ago. They found that PRMT5 methylates the nuclear factor (NF)-kB to promote proinflammation cytokines secretion, cancer progression and metastasis. This groundbreaking finding was published in the prestigious journal Proceedings of the National Academy of Sciences and featured by F1000 Prime.

Working with the Chemical Genomics and Core Facility (CGCF) at the Indiana Clinical and Translational Sciences Institute (CTSI), Lu and her team developed a high throughput platform to successfully screen for small molecule inhibitors of PRMT5, among which, Lu’s team was able to find a highly promising chemical hit, which served as the basis for this patent application.

PRMT5 inhibitors not only can be used to treat cancers, but also have expanded clinical indications, including the diseases that have hyper NF-kB activity in nature. Currently, Lu and her team are actively working with multiple collaborators to broaden the horizons of this aspect.

Lu founded EQon Pharmaceuticals with the licensed rights to further develop this drug discovery program. Matthew Martin, Ph.D., a cancer biologist and IU research scientist, works actively with Lu to expand this promising program.

“The team is currently vigorously recruiting funding to work toward the goal of identifying a lead compound with improved potency and drug-like features as the first of a new class of PRMT5- targeted anticancer drugs, paving the pathway forward for phase I clinical trials in the treatment of cancer patients,” Lu said.

Lu says she is grateful for the tremendous support from cancer center leadership, including Cancer Center Director Kelvin Lee, M.D., former director Patrick Loehrer, M.D., as well as EDT program and Cancer Drug Discovery and Development (CDDDP) leaders Mark Kelley, Ph.D., Charlie Hao, M.D./Ph.D., Xiongbin Lu, Ph.D., and Chafiq Hamdouchi, Ph.D. She also has received support from multiple cores, such as CGCF, the In Vivo Therapeutic Core (IVT), the Clinical Pharmacology Analysis Core (CPAC), and the Pancreatic Cancer Challenges and Solutions Work Group (PC-CSWG).

Lu thanked her dedicated collaborator Melissa Fishel, Ph.D., for helping with testing the PRMT5 inhibitors in 3D models. She also pointed out her appreciation for the supportive and collegial research environment provided by the Department of Pharmacology & Toxicology led by Chair Bryan Yamamoto, Ph.D.

Indiana University was ranked 53rd in the top 100 list of “Worldwide Universities Granted U.S. Utility Patents” in 2020. This patent awarded to Lu and colleagues will contribute to IU’s continued success in discovery and play a role in the 2021 worldwide patent ranking for the university.