A small-molecule inhibitor shows that pirin regulates migration of melanoma cells

A chemical array screen identifies a small-molecule inhibitor of pirin that inhibits its interaction with the oncoprotein Bcl3 and decreases the expression of the tumor mobility protein SNAI2. As a result, the compound perturbs the migration of melanoma cells that have high pirin expression levels. The discovery of small molecules that bind to a specific target and disrupt the function of proteins is an important step in chemical biology, especially for poorly characterized proteins. Human pirin is a nuclear protein of unknown function that is widely expressed in punctate subnuclear structures in human tissues. Here, we report the discovery of a small molecule that binds to pirin. We determined how the small molecule bound to pirin by solving the cocrystal structure. Either knockdown of pirin or treatment with the small molecule inhibited melanoma cell migration. Thus, inhibition of pirin by the small molecule has led to a greater understanding of the function of pirin and represents a new method of studying pirin-mediated signaling pathways.