PAC-1

PAC-1 is a procaspase-activating compound; activates procaspase-3 to produce caspase-3 (EC50 = 0.22 μM). PAC-1 enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and in mouse xenograft models. Signaling through the neuropeptide GPCR PAC(1) induces neuritogenesis via a single linear cAMP- and ERK-dependent pathway using a novel cAMP sensor. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.