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].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Cytoskeleton >> Gap Junction Protein

IC50: connexin 43 (Cx43)[1]

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]. Western Blot Analysis[1] Cell Line: Neonatal cardiomyocytes Concentration: 100 nM Incubation Time: 24 hours Result: Partially prevented the loss of Cx43 protein expression in neonatal cardiomyocytes. Apoptosis Analysis[2] Cell Line: Cx43 deficient INS-1 cells Concentration: 100 nM Incubation Time: 24 hours Result: Ameliorated cytokine-induced apoptosis associated with improved mitochondrial function.

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].

[1]. Seyed Mojtaba Ghiasi, et al. The connexin 43 regulator Rotigaptide reduces cytokine-induced cell death in human islets

[2]. Stahlhut M, et al. The antiarrhythmic peptide rotigaptide (ZP123) increases connexin 43 protein expression in neonatal rat ventricular cardiomyocytes.Cell Commun Adhes. 2006 Jan-Apr;13(1-2):21-7.

[3]. Kjølbye AL, et al. Pharmacological modulation of gap junction function with the novel compound rotigaptide: a promising new principle for prevention of arrhythmias.Basic Clin Pharmacol Toxicol. 2007 Oct;101(4):215-30.