Table 1
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Therapeutic agents developed targeting Cx43 hemichannels/gap junctions potentially for various diseases

NameMolecule typeTarget on connexinsMechanism of actionDisease indications
ALMB-0166AntibodyExtracellular domainHemichannel blockerAcute spinal cord injury [19,36]
ALMB-0168AntibodyExtracellular domainHemichannel activatorOsteosarcoma [25,37]
Mimetic peptide 5PeptideExtracellular domainChannel blockerDiabetic retinal injury [38]
Gap19PeptideIntracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [39,40]
Xentry-Gap19Cell-penetrating peptide (CPP)Intracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [40,41]
Gap26PeptideExtracellular domainChannel blockerNA [42,43]
Gap27PeptideExtracellular domainChannel blockerNA [42,43]
Xiflam
(Tonabersat)		Small moleculeNAChannel blockerDiabetic macular edema, Diabetic nephropathy, Geographic atrophy [40,44]
αCT1PeptideC-terminal domainChannel remodeling, phosphorylation mediatorDiabetic foot ulcers, skin and eye diseases [30,45,46]
Rotigaptide
(ZP123)		PeptideNAChannel modifier, gap junction couplingIschemic injury of the heart [47]
Danegaptide
(ZP1609)		PeptideNAChannel modifier, gap junction couplingMyocardial infarction [48,49]
NexagonOligonucleotideCx43 DNADecreasing Cx43 levelCorneal/skin wounds [50]
NameMolecule typeTarget on connexinsMechanism of actionDisease indications
ALMB-0166AntibodyExtracellular domainHemichannel blockerAcute spinal cord injury [19,36]
ALMB-0168AntibodyExtracellular domainHemichannel activatorOsteosarcoma [25,37]
Mimetic peptide 5PeptideExtracellular domainChannel blockerDiabetic retinal injury [38]
Gap19PeptideIntracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [39,40]
Xentry-Gap19Cell-penetrating peptide (CPP)Intracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [40,41]
Gap26PeptideExtracellular domainChannel blockerNA [42,43]
Gap27PeptideExtracellular domainChannel blockerNA [42,43]
Xiflam
(Tonabersat)		Small moleculeNAChannel blockerDiabetic macular edema, Diabetic nephropathy, Geographic atrophy [40,44]
αCT1PeptideC-terminal domainChannel remodeling, phosphorylation mediatorDiabetic foot ulcers, skin and eye diseases [30,45,46]
Rotigaptide
(ZP123)		PeptideNAChannel modifier, gap junction couplingIschemic injury of the heart [47]
Danegaptide
(ZP1609)		PeptideNAChannel modifier, gap junction couplingMyocardial infarction [48,49]
NexagonOligonucleotideCx43 DNADecreasing Cx43 levelCorneal/skin wounds [50]
Table 1
Open in new tab

Therapeutic agents developed targeting Cx43 hemichannels/gap junctions potentially for various diseases

NameMolecule typeTarget on connexinsMechanism of actionDisease indications
ALMB-0166AntibodyExtracellular domainHemichannel blockerAcute spinal cord injury [19,36]
ALMB-0168AntibodyExtracellular domainHemichannel activatorOsteosarcoma [25,37]
Mimetic peptide 5PeptideExtracellular domainChannel blockerDiabetic retinal injury [38]
Gap19PeptideIntracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [39,40]
Xentry-Gap19Cell-penetrating peptide (CPP)Intracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [40,41]
Gap26PeptideExtracellular domainChannel blockerNA [42,43]
Gap27PeptideExtracellular domainChannel blockerNA [42,43]
Xiflam
(Tonabersat)		Small moleculeNAChannel blockerDiabetic macular edema, Diabetic nephropathy, Geographic atrophy [40,44]
αCT1PeptideC-terminal domainChannel remodeling, phosphorylation mediatorDiabetic foot ulcers, skin and eye diseases [30,45,46]
Rotigaptide
(ZP123)		PeptideNAChannel modifier, gap junction couplingIschemic injury of the heart [47]
Danegaptide
(ZP1609)		PeptideNAChannel modifier, gap junction couplingMyocardial infarction [48,49]
NexagonOligonucleotideCx43 DNADecreasing Cx43 levelCorneal/skin wounds [50]
NameMolecule typeTarget on connexinsMechanism of actionDisease indications
ALMB-0166AntibodyExtracellular domainHemichannel blockerAcute spinal cord injury [19,36]
ALMB-0168AntibodyExtracellular domainHemichannel activatorOsteosarcoma [25,37]
Mimetic peptide 5PeptideExtracellular domainChannel blockerDiabetic retinal injury [38]
Gap19PeptideIntracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [39,40]
Xentry-Gap19Cell-penetrating peptide (CPP)Intracellular loopChannel blockerDry/wet macular degeneration, Diabetic retinal disease/diabetic nephropathy [40,41]
Gap26PeptideExtracellular domainChannel blockerNA [42,43]
Gap27PeptideExtracellular domainChannel blockerNA [42,43]
Xiflam
(Tonabersat)		Small moleculeNAChannel blockerDiabetic macular edema, Diabetic nephropathy, Geographic atrophy [40,44]
αCT1PeptideC-terminal domainChannel remodeling, phosphorylation mediatorDiabetic foot ulcers, skin and eye diseases [30,45,46]
Rotigaptide
(ZP123)		PeptideNAChannel modifier, gap junction couplingIschemic injury of the heart [47]
Danegaptide
(ZP1609)		PeptideNAChannel modifier, gap junction couplingMyocardial infarction [48,49]
NexagonOligonucleotideCx43 DNADecreasing Cx43 levelCorneal/skin wounds [50]
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