| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
Danegaptide hydrochloride targets connexin 43 (Cx43)-mediated gap junctions. Gap junctions are channels that allow direct cell-to-cell communication, and Cx43 is the predominant connexin in cardiac tissue. By modulating Cx43 gap junction function, danegaptide enhances cell-to-cell communication and prevents electrical uncoupling during metabolic stress. This mechanism underlies its antiarrhythmic effect. The compound's selectivity for gap junctions over other targets contributes to its therapeutic potential for cardiovascular pathologies.
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| ln Vitro |
Danegaptide (GAP-134, Compound 9f; 0.01 nM-100 μM) is designed to decrease dye food in C6 neuroastroma cells that have been cultivated [1].
In vitro, danegaptide hydrochloride demonstrates high potency in preventing conduction velocity slowing at concentrations of 10-100 nM in cardiac tissue strips, ensuring clean electrophysiology data. The compound's activity as a gap junction modifier has been characterized in various in vitro systems. It enhances gap junction communication and prevents electrical uncoupling under conditions of metabolic stress. The compound's potency and selectivity have been established through rigorous in vitro pharmacological characterization. |
| ln Vivo |
The effectiveness of diengaptide (GAP-134, compound 9f) was assessed in vivo using a CaCl2 mouse model. Danegaptide (GAP-134) is bioactive and decreases atrial fibrillation in a dog model. Danegaptide (GAP-134) in rats at a mean heart rate concentration of 250 nM considerably prolongs the ischemia state following infusion of CaCl2[1]. Heart rate, arterial blood pressure, and other electrocardiogram (ECG) parameters are unaffected by danegaptide. Danegaptide is a strong antiarrhythmic drug that causes arrhythmias brought on by reperfusion or cardiovascular disease in beagle dogs who have been given a barbiturate and made unconscious [2].
In vivo, danegaptide hydrochloride has demonstrated superior cardioprotection, reducing myocardial infarct size by 46% in porcine models compared to vehicle and ischemic postconditioning. The compound achieves therapeutic plasma levels (~250 nM) in canine models, enabling chronic dosing studies without parenteral administration. Its oral bioavailability supports its potential for treating atrial fibrillation and myocardial ischemia/reperfusion injury. The compound's antiarrhythmic effect has been validated in various animal models. |
| Enzyme Assay |
In vitro receptor binding and functional assays for danegaptide hydrochloride involve studying its effects on gap junction communication using cells expressing Cx43. Gap junction function is assessed by measuring dye transfer or electrical coupling between cells. The compound's ability to prevent conduction velocity slowing is evaluated using cardiac tissue strips or cultured cardiomyocytes. Binding affinity to Cx43 or other gap junction components may be assessed using radioligand binding or surface plasmon resonance. These assays establish the compound's potency and selectivity as a gap junction modifier.
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| Cell Assay |
In vitro cell-based assays for danegaptide hydrochloride involve treating cardiomyocytes or other cells expressing Cx43 with the compound to assess its effects on gap junction function. Cells are subjected to metabolic stress (e.g., hypoxia, ischemia), and the compound's ability to prevent electrical uncoupling is measured. Dye transfer assays using fluorescent dyes (e.g., Lucifer Yellow) quantify gap junction permeability. Electrophysiological recordings measure cell-to-cell electrical coupling. These cellular assays provide mechanistic insights into the compound's gap junction-modifying activity.
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| Animal Protocol |
In vivo animal experiments for danegaptide hydrochloride have been conducted in porcine models of myocardial ischemia/reperfusion injury. The compound is administered orally or intravenously, and infarct size is measured as the primary efficacy endpoint. In canine models, therapeutic plasma levels (~250 nM) are achieved following oral administration. Models of atrial fibrillation are used to assess antiarrhythmic efficacy. Pharmacokinetic-pharmacodynamic relationships are established to guide dose selection. These studies support the compound's potential for cardiovascular indications.
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| ADME/Pharmacokinetics |
Danegaptide hydrochloride has a molecular weight of 327.76 and a molecular formula of C14H18ClN3O4. It is a small modified dipeptide with oral bioavailability. The compound is soluble in DMSO and is typically stored in dry, dark conditions at 0-4°C for short-term storage or -20°C for long-term storage. Its oral bioavailability (~250 nM in canine models) supports chronic dosing without parenteral administration. Pharmacokinetic parameters such as half-life and clearance have been characterized in animal models.
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| Toxicity/Toxicokinetics |
Available toxicity data for danegaptide hydrochloride is characteristic of gap junction modifiers. The compound is generally well-tolerated at therapeutic doses, with a safety margin sufficient for cardiovascular applications. Preclinical toxicology studies have been conducted in animal models to establish the safety profile. The compound's selectivity for gap junctions over other targets contributes to its favorable safety profile. Standard safety precautions should be taken when handling the compound in research settings.
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| References |
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| Additional Infomation |
Danegaptide hydrochloride is a potent, selective, orally active second-generation gap junction modifier targeting Cx43-mediated gap junctions. It is also known as GAP-134 or ZP-1609. The compound reduces myocardial infarct size by 46% in porcine models and achieves therapeutic plasma levels (~250 nM) in canine models. It prevents conduction velocity slowing at 10-100 nM in cardiac tissue. Danegaptide has potential for treating atrial fibrillation and myocardial ischemia/reperfusion injury.
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| Molecular Formula |
C14H18CLN3O4
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| Molecular Weight |
327.7634
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| Exact Mass |
327.099
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| CAS # |
943133-81-1
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| Related CAS # |
Danegaptide;943134-39-2
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| PubChem CID |
44563896
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| Appearance |
White to off-white solid powder
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| LogP |
1.444
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
420
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@H](CN([C@@H]1C(=O)O)C(=O)CN)NC(=O)C2=CC=CC=C2.Cl
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| InChi Key |
AHXPMNACLWKFRQ-DHXVBOOMSA-N
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| InChi Code |
InChI=1S/C14H17N3O4.ClH/c15-7-12(18)17-8-10(6-11(17)14(20)21)16-13(19)9-4-2-1-3-5-9;/h1-5,10-11H,6-8,15H2,(H,16,19)(H,20,21);1H/t10-,11+;/m1./s1
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| Chemical Name |
(4R)-Glycyl-4-(benzoylamino)-L-proline hydrochloride
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| Synonyms |
Danegaptide GAP-134 HCl GAP-134-HCl GAP134HCl GAP 134 HCl GAP134 hydrochloride
GAP-134 hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 55 mg/mL (~167.81 mM)
H2O : ≥ 50 mg/mL (~152.55 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (305.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0510 mL | 15.2551 mL | 30.5101 mL | |
| 5 mM | 0.6102 mL | 3.0510 mL | 6.1020 mL | |
| 10 mM | 0.3051 mL | 1.5255 mL | 3.0510 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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