Journal
FUTURE MEDICINAL CHEMISTRY
Volume 13, Issue 4, Pages 379-392Publisher
Newlands Press Ltd
DOI: 10.4155/fmc-2020-0291
Keywords
amphiphilic kanamycin; connexin; gap-junction protein; ischemia; wound healing
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Gap-junction channels formed by connexin hemichannels are crucial for intercellular communication, but abnormal activity can lead to diseases. Amphiphilic kanamycins, especially towards connexin 43 inhibition, show promising potential with low cytotoxicity.
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.
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