Danegaptide Hydrochloride |
Catalog No.GC35807
One-Click Copy Product Info
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Danegaptide Hydrochloride is a potent, selective, and orally active gap-junction modifier.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 943133-81-1
Sample solution is provided at 25 µL, 10mM.
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Danegaptide Hydrochloride is a potent, selective, and orally active gap-junction modifier[1]. Danegaptide Hydrochloride optimizes intercellular communication in cardiac cells by regulating electrical signal transduction, thereby restoring or improving normal heart rhythm[2]. Danegaptide Hydrochloride can reduce the occurrence of arrhythmic events such as atrial fibrillation[3]. Danegaptide Hydrochloride can protect the heart from harmful stimuli like ischemia/reperfusion injury[4].
In vitro, pretreatment of human proximal tubule epithelial cells (hPTECs) with Danegaptide Hydrochloride (50–100nM) for 48 hours, followed by stimulation with TGFβ1 (10ng/ml), significantly blocked connexin 43 (Cx43)-mediated hemichannel activity and inhibited ATP release[5]. Pretreatment of rat retinal vascular endothelial cells (RRECs) with Danegaptide Hydrochloride (100nM) for 3–7 days, followed by high glucose (30mM) stimulation, significantly maintained gap junction intercellular communication (GJIC) activity[6].
In vivo, intraperitoneal administration of Danegaptide Hydrochloride (3mg/kg twice daily) starting from day 3 after middle cerebral artery occlusion (MCAO) and continuing for two weeks in MCAO rats significantly improved neurological behavior, increased dendritic spine density in the hippocampal CA1 and DG regions, alleviated synaptic ultrastructural damage, and upregulated the expression of synaptic plasticity markers SYN and GAP-43, promoting synaptic plasticity and neurological functional recovery after focal cerebral ischemia[7]. Oral administration of Danegaptide Hydrochloride (5mg/kg/day) via drinking water to Scn5a+/- mice from 45 weeks of age until 60 weeks significantly increased the expression and Ser368 phosphorylation of cardiac connexin 43 (Cx43), prevented Cx43 mislocalization, suppressed the development of ventricular fibrosis, and reduced abnormal proliferation of cardiac fibroblasts, thereby inhibiting age-dependent myocardial fibrosis progression[8].
References:
[1] Dhein S, Hagen A, Jozwiak J, et al. Improving cardiac gap junction communication as a new antiarrhythmic mechanism: the action of antiarrhythmic peptides. Naunyn Schmiedebergs Arch Pharmacol. 2010 Mar;381(3):221-34.
[2] Piatnitski Chekler EL, Butera JA, et al. Discovery of a class of potent gap-junction modifiers as novel antiarrhythmic agents. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4551-4.
[3] Rossman EI, Liu K, Morgan GA, et al. The gap junction modifier, GAP-134 [(2S,4R)-1-(2-aminoacetyl)-4-benzamido-pyrrolidine-2-carboxylic acid], improves conduction and reduces atrial fibrillation/flutter in the canine sterile pericarditis model. J Pharmacol Exp Ther. 2009 Jun;329(3):1127-33.
[4] Hennan JK, Swillo RE, Morgan GA, et al. GAP-134 ([2S,4R]-1-[2-aminoacetyl]4-benzamidopyrrolidine-2-carboxylic acid) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs. J Cardiovasc Pharmacol Ther. 2009 Sep;14(3):207-14.
[5] Squires PE, Price GW, Mouritzen U, et al. Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney. Int J Mol Sci. 2021 Mar 10;22(6):2809.
[6] Kim D, Mouritzen U, Larsen BD, et al. Inhibition of Cx43 gap junction uncoupling prevents high glucose-induced apoptosis and reduces excess cell monolayer permeability in retinal vascular endothelial cells. Exp Eye Res. 2018 Aug;173:85-90.
[7] Yang K, Zhou Y, Zhou L, et al. Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134. Front Neurol. 2020 Aug 26;11:888.
[8] Patin J, Castro C, Steenman M, et al. Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a+/- mice. Pharmacol Res. 2020 Sep;159:104922.
| Cell experiment [1]: | |
Cell lines | Rat Retinal Endothelial Cells (RRECs) |
Preparation Method | RRECs were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), antimycotics, and antibiotics at 37°C, 5% CO₂. Cells were grown in high glucose (HG; 30mM) medium for 3, 5, or 7 days until confluence. Cells grown in HG medium were exposed to Danegaptide Hydrochloride (100nM). |
Reaction Conditions | 100nM; 3, 5, and 7 days. |
Applications | Danegaptide Hydrochloride significantly preserved gap junction intercellular communication (GJIC) activity in RRECs under high glucose condition. Danegaptide Hydrochloride significantly prevented high glucose-induced apoptosis, also significantly reduced high glucose-induced excess cell monolayer permeability. |
| Animal experiment [2]: | |
Animal models | Sprague-Dawley rats |
Preparation Method | Rats were subjected to focal cerebral ischemia via middle cerebral artery occlusion (MCAO). Danegaptide Hydrochloride was dissolved in distilled water and administered intraperitoneally at a dose of 3mg/kg twice daily, starting from day 3 post-ischemia until sacrifice. |
Dosage form | 3mg/kg; i.p. |
Applications | Danegaptide Hydrochloride administration significantly improved neurological behavior scores in balance beam walking and Y-maze tests, increased dendritic spine density in hippocampal CA1 and DG regions, alleviated synaptic ultrastructure destruction, and upregulated the expression of synaptic plasticity markers synaptophysin (SYN) and growth-associated protein-43 (GAP-43) compared to the MCAO group. |
References: | |
| Cas No. | 943133-81-1 | SDF | |
| Canonical SMILES | O=C(N[C@H]1CN(C(CN)=O)[C@H](C(O)=O)C1)C2=CC=CC=C2.[H]Cl | ||
| Formula | C14H18ClN3O4 | M.Wt | 327.76 |
| Solubility | Water: ≥ 75 mg/mL (228.83 mM); DMSO: ≥ 55 mg/mL (167.81 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.051 mL | 15.2551 mL | 30.5101 mL |
| 5 mM | 610.2 μL | 3.051 mL | 6.102 mL |
| 10 mM | 305.1 μL | 1.5255 mL | 3.051 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)