1.C.59.1.1
CPE (Clostridium perfringens Enterotoxin) has been used for suicide gene therapy for selective treatment of claudin-3-and-4-overexpressing tumors (Walther et al., 2011).  It can be used as an oncoleaking/tumor eradication agent as this pore-forming protein exerts specific and rapid toxicity towards claudin-3- and -4-overexpressing cancers (Pahle et al. 2015). The crystal structure of Clostridium perfringens enterotoxin displays features of beta-pore-forming toxins (Kitadokoro et al., 2011). The N-terminal region (nCPE) mediates the cytotoxic effect through pore formation in the plasma membrane of the mammalian host cell. The C-terminal region (cCPE) binds to the second extracellular loop of a subset of claudins, Claudin-3 and claudin-4, with high affinity (Veshnyakova et al., 2010). cCPE is not cytotoxic but is a potent modulator of tight junctions. The toxin forms highly cation-selective channels in lipid bilayers (Benz and Popoff 2018). Mepacrine inhibits CPE-induced electrophysiology effects in artificial lipid bilayers lacking CPE receptors by blocking subunit oligomerization and pore formation (Freedman et al. 2017).