Cancer Research Technology (CRT), the development and commercialization arm of Cancer Research UK, recently announced a licensing agreement with Merck (MSD) to develop and commercialize protein arginine methyltransferase 5 (PRMT5) inhibitors. CRT, a subsidiary of Cancer Research UK, entered into this agreement with MSD (Germany) on behalf the Australian Cooperative Research Center for Cancer Therapeutics (CTx), who developed the investigational PRMT5 inhibitors based on pioneering work by Professor Stephen Jane of Monash University (Melbourne, Australia) and funding from a Seeding Drug Discovery Award provided by the Wellcome Trust (UK). The total value of the deal if all milestones are met is $0.5B, with the majority returned to CTx and its Australian research partners. The Australian group used BellBrook’s Transcreener® EPIGEN Methyltransferase Assay extensively in developing the novel PRMT5 inhibitors.
The PRMT5 protein, which catalyzes methyl group transfers to the amino acid arginine, can mark a variety of genes involved in the cellular processes that it affects. In PRMT5-mediated methylation of the tumor suppressor p53, these epigenetic mutations void the anti-carcinogenic effects routinely observed for the wildtype p53 gene. In nine out of ten cancers, oncogene p53 is faulty; in cancers with lethal prognoses, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), melanoma, lung, and breast, PRMT5 levels are elevated.
Inhibitors of the culprit PRMT5 can alter the outcome by switching on genes, potentially restoring original function or modifying disease progression. Thus, PRMT5 inhibitors become excellent therapeutic candidates for cancerous and non-cancerous disorders, including the blood disorders involving hemoglobin (sickle cell anemia and beta thalassemia). This multinational collaboration, with the expertise of all parties involved, has excellent potential to push epigenetic treatment options featuring methyltransferase inhibitors into the clinic and out to those who need it most.