Danegaptide (GAP-134 and ZP-1609) is a novel, potent, selective and orally bioavailable small molecule gap-junction modifier with a potential for the treatment of atrial fibrillation.

Physicochemical Properties

Molecular Weight	291.30248
Exact Mass	291.122
CAS #	943134-39-2
Related CAS #	Danegaptide Hydrochloride;943133-81-1
PubChem CID	16656685
Appearance	Typically exists as solid at room temperature
LogP	0.642
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	21
Complexity	420
Defined Atom Stereocenter Count	2
SMILES	O=C(N[C@H]1CN(C(CN)=O)[C@H](C(O)=O)C1)C2=CC=CC=C2
InChi Key	BIZKIHUJGMSVFD-MNOVXSKESA-N
InChi Code	InChI=1S/C14H17N3O4/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)/t10-,11+/m1/s1
Chemical Name	(2S,4R)-4-benzamido-1-glycylpyrrolidine-2-carboxylic acid
Synonyms	ZP1609 ZP-1609 ZP 1609 GAP-134 GAP 134 GAP134
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	Cultured C6 glioma cells' dye uptake is dose-dependently reduced by diegaptide (GAP-134, compound 9f; 0.01 nM-100 μM) [1].
ln Vivo	After oral treatment, the in vivo effectiveness of Danegaptide (GAP-134, compound 9f) was assessed in the mouse CaCl2 model. Danegaptide dramatically increases the length of conduction block following CaCl2 infusion in mice at oral dosages of 5–20 mg/kg [1]. In a dog model, danegaptide (GAP-134) decreases atrial fibrillation and is bioactive after oral treatment, with a mean plasma concentration of 250 nM. Heart rate, arterial blood pressure, and other electrocardiogram (ECG) parameters are unaffected by digaptide. For the treatment of ischemia/reperfusion-induced cardiac arrhythmias in barbiturate-anesthetized open-chest beagle dogs, diregaptide is a powerful antiarrhythmic drug [2].
References	[1]. Discovery of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride (GAP-134)13, an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation. J Med Chem. 2009 Feb 26;52(4):. [2]. Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 2011 Jun;163(3):469-83.
Additional Infomation	Danegaptide is a dipeptide. Danegaptide has been investigated for the treatment of Focus of Study is STEMI. See also: Rotigaptide (annotation moved to). Mechanism of Action Danegaptide, a small modified dipeptide, is a selective second generation gap junction modifier with oral bioavailability. Danegaptide prevents postoperative atrial fibrillation (AF) and chronic AF in large animal models. In a canine model of acute sterile pericarditis, Danegaptide significantly reduced AF duration and overall AF burden. Danegaptide has a similar mechanism of action to its parent compound rotigaptide. Rotigaptide is a synthetic antiarrhythmic peptide (AAP) analogue which has been tested in vitro which shows prevention of prevents metabolic stress-induced atrial conduction velocity (CV) and rapidly reverts established atrial CV slowing. Rogitapeptide enhances gap junction conductance and coupling, increasing the amount of small molecules such as ions, metabolites and secondary messengers passing from one cell to another.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.4329 mL	17.1644 mL	34.3289 mL
	5 mM	0.6866 mL	3.4329 mL	6.8658 mL
	10 mM	0.3433 mL	1.7164 mL	3.4329 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.