Rotigaptide is a novel and specific modulator of Cx43 and is a potent AAP. Rotigaptide prevents the uncoupling of Cx43-mediated gap junction communication and normalizes cell-to-cell communication during acute metabolic stress.

Rotigaptide (100 nM; 24 hours) does not affect apoptosis of INS-1 cells itself but positively influences the cycloheximide-mediated decrease in Cx43 protein levels in cultured neonatal ventricular myocytes, and significantly decreases apoptosis in cytokine-exposed INS-1 cells by approximately 10% at IL-1b concentrations above 15 pg/ml in rat insulin-producing INS-1 cells [1][2].

Rotigaptide (intravenous administration; 300 mg/kg; single dose) in mice and rats, and (continuous intravenous infusion; 100 mg/kg in rats, 10 mg/kg in dogs; 5-14 days) is non-toxic and well-tolerated, with no compound-related effects or histological toxicity in escalating dose studies [3].