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 INS-1 cell apoptosis itself. Rotigaptide (100 nM; 24 hours) has a positive effect on the cycloheximide-mediated decrease in Cx43 protein levels in cultured neonatal ventricular myocytes. And it obviously decreases apoptosis in cytokine-exposed cells ~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) treatment in mice and rats does not cause toxicity in either species. Rotigaptide (continuous intravenous infusion; 5-14 days) in rats (100 mg/kg) and dogs (10 mg/kg) is well tolerated and produces no compound-related effects or histological toxicological findings in escalating dose studies [3].