Cx43 hemichannel inhibitor D4(R) is a potent and selective blocker of Cx43 hemichannels with IC50 of 5 nM, without inhibiting gap junction channels formed by the same connexin, and does not block Cx36 hemichannels.
D4(R) shows blocking activity against both Cx26 and Cx43.
D4(R) inhibits the Cx hemichannels but not Cx gap junctions using the pilocarpine mouse model of temporal lobe epilepsy (TLE).
D4(R) caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity in vitro.
D4(R) effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate in vivo.
D4(R) has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine in vivo.
