Developing quinoline-based secretagogues for prostate apoptosis response-4 protein (Par-4) as potential antineoplastic agents

Secretagogues bearing a 3-arylquinoline scaffold-induced secretory events in normal cells that released the tumor suppressor protein, prostate apoptosis response-4 protein (Par-4) sequestered by the intermediary filament protein, vimentin. The secretion of the Par-4 protein and its binding to a selective, cell-surface receptor GRP78 subsequently triggered paracrine apoptosis in cancer cells. These findings provided a rationale for the study of Par-4 secretagogues as potential agents for the inhibition of tumor growth. Developing secretagogues with these scaffolds, determining vimentin as the biomolecular target, using molecular dynamics to model arylquin binding to vimentin, and understanding the secretion of Par-4 and its apoptotic effects held promise as a new approach for small-molecule interventions as potential treatments for cancer.