[CAS NO. 355151-12-1] Rotigaptide
PRODUCTS SPECIFICATIONS [355151-12-1]
DESCRIPTION [355151-12-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 617.65 |
| Molecular Formula | C28H39N7O9 |
| SMILES | O=C(N)CNC([C@@H](C)NC(CNC([C@@H]1N(C([C@@H]2N(C([C@@H](CC3=CC=C(O)C=C3)NC(C)=O)=O)CCC2)=O)C[C@@H](O)C1)=O)=O)=O |
Summary
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. |
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00137293 | Wyeth is now a wholly owned subsidiary of Pfizer |
Arrhythmia
|
November 2005 | Phase 2 |
| NCT00137332 | Wyeth is now a wholly owned subsidiary of Pfizer |
Arrhythmia
|
November 2005 | Phase 2 |
| NCT00901563 | University of Edinburgh|Chief Scientist Office of the Scottish Government|NHS Lothian |
Vascular Disease|Heart Disease
|
March 2009 | Not Applicable |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 200 mg/mL ( 323.81 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.6190 mL | 8.0952 mL | 16.1904 mL |
| 5 mM | 0.3238 mL | 1.6190 mL | 3.2381 mL |
| 10 mM | 0.1619 mL | 0.8095 mL | 1.6190 mL |
References
- [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.