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MedKoo Cat#: 563931 | Name: Danegaptide HCl
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Danegaptide, also known as GAP-134 and ZP1609, is an orally active small molecule gap-junction modifier for the treatment of atrial fibrillation. Danegaptide mproves conduction and reduces atrial fibrillation/flutter in the canine sterile pericarditis model. Danegaptide prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs.

Chemical Structure

Danegaptide HCl
Danegaptide HCl
CAS#943133-81-1 (HCl)

Theoretical Analysis

MedKoo Cat#: 563931

Name: Danegaptide HCl

CAS#: 943133-81-1 (HCl)

Chemical Formula: C14H18ClN3O4

Exact Mass: 0.0000

Molecular Weight: 327.77

Elemental Analysis: C, 51.30; H, 5.54; Cl, 10.82; N, 12.82; O, 19.52

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 650.00 2 Weeks
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Related CAS #
943134-39-2 (free base) 943133-81-1 (HCl)
Synonym
GAP-134 HCl; GAP-134; GAP134; ZP1609; ZP-1609; ZP 1609; Danegaptide HCl; Danegaptide hydrochloride;
IUPAC/Chemical Name
(4R)-Glycyl-4-(benzoylamino)-L-proline hydrochloride
InChi Key
AHXPMNACLWKFRQ-DHXVBOOMSA-N
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
SMILES Code
O=C(O)[C@H]1N(C(CN)=O)C[C@H](NC(C2=CC=CC=C2)=O)C1.[H]Cl
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.03.00
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Danegaptide Hydrochloride (GAP-134 Hydrochloride, ZP1609 Hydrochloride) is a potent, selective and orally active gap-junction modifier with an antiarrhythmic effect.
In vitro activity:
The effects of ZP1609 on the function of murine sub-sarcolemmal mitochondria (SSM, containing Cx43) and interfibrillar mitochondria (IFM, lacking Cx43) were studied. Murine isolated cardiomyocytes were subjected to simulated I/R without and with ZP1609 (applied during I/R or at the onset of reperfusion only). ZP1609 inhibited ADP-stimulated respiration and ATP production in SSM and IFM. Potassium uptake was also enhanced in IFM. The number of rod-shaped cardiomyocytes was increased by ZP1609 (10 μM) when administered either during I/R or reperfusion. ZP1609 altered the phosphorylation of proteins contributing to the protection against I/R injury. The protective effect was independent of mitochondrial Cx43, as ZP1609 exerts its effects in Cx43-containing SSM and Cx43-lacking IFM. Reference: Br J Pharmacol. 2017 Jul;174(13):2060-2073. https://pubmed.ncbi.nlm.nih.gov/28369703/
In vivo activity:
To investigate whether danegaptide could be protective in stroke, mice were therapeutically treated with the drug under an ischemia/reperfusion stroke model tMCAO. After 50 min of ischemia, saline or 75 µg/kg of danegaptide was administered via tail vein injection. After 60 min of ischemia, reperfusion was introduced and mice were treated with subsequent danegaptide at 1, 2 and 3 h after the initial injection. A significant (p = 0.0018) 42.2% reduction in infarct volume was measured in those mice treated with danegaptide, compared to controls (Figure 4). It is shown here that administration of danegaptide during tMCAO is neuroprotective. Reference: Biomolecules. 2020 Mar; 10(3): 353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175267/
Solvent mg/mL mM
Solubility
DMSO 55.0 167.81
H2O 75.0 228.83
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 327.77 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Squires PE, Price GW, Mouritzen U, Potter JA, Williams BM, Hills CE. Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney. Int J Mol Sci. 2021 Mar 10;22(6):2809. doi: 10.3390/ijms22062809. PMID: 33802083; PMCID: PMC7999212. 2. Boengler K, Bulic M, Schreckenberg R, Schlüter KD, Schulz R. The gap junction modifier ZP1609 decreases cardiomyocyte hypercontracture following ischaemia/reperfusion independent from mitochondrial connexin 43. Br J Pharmacol. 2017 Jul;174(13):2060-2073. doi: 10.1111/bph.13804. Epub 2017 May 10. PMID: 28369703; PMCID: PMC5466543. 3. Freitas-Andrade M, Bechberger J, Wang J, Yeung KKC, Whitehead SN, Hansen RS, Naus CC. Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice. Biomolecules. 2020 Feb 26;10(3):353. doi: 10.3390/biom10030353. PMID: 32110860; PMCID: PMC7175267. 4. Amdisen C, Keller AK, Hansen RS, Nørregaard R, Krag SP, Møldrup U, Pedersen M, Jespersen B, Birn H. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model. PLoS One. 2016 Oct 19;11(10):e0164109. doi: 10.1371/journal.pone.0164109. PMID: 27760220; PMCID: PMC5070773.
In vitro protocol:
1. Squires PE, Price GW, Mouritzen U, Potter JA, Williams BM, Hills CE. Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney. Int J Mol Sci. 2021 Mar 10;22(6):2809. doi: 10.3390/ijms22062809. PMID: 33802083; PMCID: PMC7999212. 2. Boengler K, Bulic M, Schreckenberg R, Schlüter KD, Schulz R. The gap junction modifier ZP1609 decreases cardiomyocyte hypercontracture following ischaemia/reperfusion independent from mitochondrial connexin 43. Br J Pharmacol. 2017 Jul;174(13):2060-2073. doi: 10.1111/bph.13804. Epub 2017 May 10. PMID: 28369703; PMCID: PMC5466543.
In vivo protocol:
1. Freitas-Andrade M, Bechberger J, Wang J, Yeung KKC, Whitehead SN, Hansen RS, Naus CC. Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice. Biomolecules. 2020 Feb 26;10(3):353. doi: 10.3390/biom10030353. PMID: 32110860; PMCID: PMC7175267. 2. Amdisen C, Keller AK, Hansen RS, Nørregaard R, Krag SP, Møldrup U, Pedersen M, Jespersen B, Birn H. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model. PLoS One. 2016 Oct 19;11(10):e0164109. doi: 10.1371/journal.pone.0164109. PMID: 27760220; PMCID: PMC5070773.
1: Squires PE, Price GW, Mouritzen U, Potter JA, Williams BM, Hills CE. Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney. Int J Mol Sci. 2021 Mar 10;22(6):2809. doi: 10.3390/ijms22062809. PMID: 33802083; PMCID: PMC7999212. 2: Freitas-Andrade M, Bechberger J, Wang J, Yeung KKC, Whitehead SN, Hansen RS, Naus CC. Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice. Biomolecules. 2020 Feb 26;10(3):353. doi: 10.3390/biom10030353. PMID: 32110860; PMCID: PMC7175267. 3: Engstrøm T, Nepper-Christensen L, Helqvist S, Kløvgaard L, Holmvang L, Jørgensen E, Pedersen F, Saunamaki K, Tilsted HH, Steensberg A, Fabricius S, Mouritzen U, Vejlstrup N, Ahtarovski KA, Göransson C, Bertelsen L, Kyhl K, Olivecrona G, Kelbæk H, Lassen JF, Køber L, Lønborg J. Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial. Heart. 2018 Oct;104(19):1593-1599. doi: 10.1136/heartjnl-2017-312774. Epub 2018 Mar 30. PMID: 29602883. 4: DeLalio LJ, Isakson BE. ZP1609/danegaptide and mitochondrial connexin hemichannels: a harbinger for peptide drug design. Br J Pharmacol. 2017 Aug;174(15):2606-2607. doi: 10.1111/bph.13891. Epub 2017 Jul 9. PMID: 28567717; PMCID: PMC5513857. 5: Amdisen C, Keller AK, Hansen RS, Nørregaard R, Krag SP, Møldrup U, Pedersen M, Jespersen B, Birn H. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model. PLoS One. 2016 Oct 19;11(10):e0164109. doi: 10.1371/journal.pone.0164109. PMID: 27760220; PMCID: PMC5070773. 6: Skyschally A, Walter B, Schultz Hansen R, Heusch G. The antiarrhythmic dipeptide ZP1609 (danegaptide) when given at reperfusion reduces myocardial infarct size in pigs. Naunyn Schmiedebergs Arch Pharmacol. 2013 May;386(5):383-91. doi: 10.1007/s00210-013-0840-9. Epub 2013 Feb 9. PMID: 23397587. 7: Wang JSH, Freitas-Andrade M, Bechberger JF, Naus CC, Yeung KK, Whitehead SN. Matrix-assisted laser desorption/ionization imaging mass spectrometry of intraperitoneally injected danegaptide (ZP1609) for treatment of stroke- reperfusion injury in mice. Rapid Commun Mass Spectrom. 2018 Jun 30;32(12):951-958. doi: 10.1002/rcm.8115. PMID: 29575411. 8: Zhu Y, Li N, Huang M, Chen X, An YA, Li J, Zhao S, Funcke JB, Cao J, He Z, Zhu Q, Zhang Z, Wang ZV, Xu L, Williams KW, Li C, Grove K, Scherer PE. Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention. Acta Pharm Sin B. 2022 Jul;12(7):3063-3072. doi: 10.1016/j.apsb.2022.02.020. Epub 2022 Feb 26. PMID: 35865093; PMCID: PMC9293664. 9: Patin J, Castro C, Steenman M, Hivonnait A, Carcouët A, Tessier A, Lebreton J, Bihouée A, Donnart A, Le Marec H, Baró I, Charpentier F, Derangeon M. Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a+/- mice. Pharmacol Res. 2020 Sep;159:104922. doi: 10.1016/j.phrs.2020.104922. Epub 2020 May 25. PMID: 32464326. 10: Johnstone SR, Isakson BE. 'Gaps' in targeted ischaemic injury therapies in ST-elevation myocardial infarction. Heart. 2018 Oct;104(19):1557-1558. doi: 10.1136/heartjnl-2018-313084. Epub 2018 Mar 30. PMID: 29602882. 11: Kim D, Mouritzen U, Larsen BD, Roy S. 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. doi: 10.1016/j.exer.2018.05.003. Epub 2018 May 9. PMID: 29750972. 12: Thomsen AF, Bertelsen L, Jøns C, Jabbari R, Lønborg J, Kyhl K, Göransson C, Nepper-Christensen L, Atharovski K, Ekström K, Tilsted HH, Pedersen F, Køber L, Engstrøm T, Vejlstrup N, Jacobsen PK. Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction. Europace. 2023 Mar 30;25(3):978-988. doi: 10.1093/europace/euac256. PMID: 36576342; PMCID: PMC10062367. 13: Boengler K, Bulic M, Schreckenberg R, Schlüter KD, Schulz R. The gap junction modifier ZP1609 decreases cardiomyocyte hypercontracture following ischaemia/reperfusion independent from mitochondrial connexin 43. Br J Pharmacol. 2017 Jul;174(13):2060-2073. doi: 10.1111/bph.13804. Epub 2017 May 10. PMID: 28369703; PMCID: PMC5466543.