Advances in the development of connexin hemichannel inhibitors selective toward Cx43

Gap-junction channels formed by two connexin hemichannels play diverse and pivotal roles in intercellular communication and regulation. Normally hemichannels at the plasma membrane participate in autocrine and paracrine signaling, but abnormal increase in their activity can lead or contribute to various diseases. Selective inhibitors toward connexin hemichannels are of great interest. Among more than 20 identified isoforms of connexins, connexin 43 (Cx43) attracts the most interest due to its prevalence and link to cell damage in many disorders or diseases. Traditional antibacterial kanamycin decorated with hydrophobic groups yields amphiphilic kanamycins that show low cytotoxicity and prominent inhibitory effect against Cx43. This review focuses on the development of amphiphilic kanamycins as connexin hemichannel inhibitors and their future perspective.