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Zifogaptide (aCT1) is a synthetic peptide developed by Xequel Bio that mimics the carboxyl-terminus of Connexin 43 (Cx43). It is designed to stabilize gap and tight junctions and modulate inflammation at injury sites. The peptide works by competitively binding to the PDZ2 domain of the scaffolding protein Zonula Occludens-1 (ZO-1), which prevents the sequestration of Cx43 into hemichannels and promotes its incorporation into functional gap junctions. This mechanism helps maintain tissue integrity and reduces vascular permeability. The aerosolized formulation is specifically being developed for the treatment of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) to mitigate pulmonary edema and hyper-inflammation by reinforcing the alveolar-capillary barrier.
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