Progression of Metarrestin that Reduces PNC Prevalence and Elucidation of its Mechanism of Action

National Center For Advancing Translational Sciences

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Abstract

The collaborative team, through high-throughput screening followed by chemical optimization, developed a compound, metarrestin, which disrupts the perinuclear compartment (PNC) in different types of cancer cells. The PNC is a structure located within the nuclei of cancer cells and associated with metastatic capacity. Metarrestin inhibited tumor invasion and metastasis in multiple mouse models of cancer and prolonged the animal's survival, suggesting its potential relevance for translation to patients. During this period, the team has continued to investigate the mechanism of action of metarrestin using a set of in vitro and in vivo tools and pursued genomic and proteomic approaches to aid in this investigation. New analogues generated through structure-activity relationship studies were tested for their effects on metastatic cancer cells.