Rotigaptide

Rotigaptide (ZP123) is a novel and specific modulator of connexin 43 (Cx43). Rotigaptide prevents the uncoupling of Cx43-mediated gap junction communication and normalizes cell-to-cell communication during acute metabolic stress. Rotigaptide is a potent antiarrhythmic peptide (AAP) with improved stability and has the potential for the investigation of cardiac arrhythmias-specifically?atrial fibrillation^[1][2]. IC50 & Target: IC50: connexin 43 (Cx43)^[1] In Vitro: Rotigaptide (100 nM; 24 hours) has a positive effect on cycloheximide-mediated decrease in Cx43 protein levels in cultured neonatal ventricular myocytes^[1].
Rotigaptide (100 nM; 24 hours) dose not affect INS-1 cell apoptosis itself. And it significantly reduces apoptosis in cytokine-exposed cells ~10% at IL-1b concentrations above 15 pg/ml in rat insulin-producing INS-1 cells^[2].
In Vivo: Rotigaptide (intravenous administration; 300 mg/kg; single dose) treatment in mice and rats does not result in toxicity in either species.
In escalating dose studies, Rotigaptide (continuous intravenous infusion; 5-14 days) in rats (100 mg/kg) and dogs (10 mg/kg) are well tolerated and produces no compound-related effects or histological toxicological findings^[3].