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Danegaptide

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Chemical Structure| 943134-39-2 同义名 : Gap-134;ZP 1609
CAS号 : 943134-39-2
货号 : A680718
分子式 : C14H17N3O4
纯度 : 98%
分子量 : 291.303
MDL号 : MFCD16619374
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Gap junction uncoupling can alter conduction pathways and promote cardiac re-entry mechanisms that potentiate many supraventricular arrhythmias, such as atrial fibrillation (AF) and atrial flutter (AFL)[3]. GAP-134 is a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue[4]. Gap-134 (danegaptide), between 45 and 60 weeks, increased Cx43 expression and phosphorylation on serine 368 and prevented Cx43 delocalization. Furthermore, we found that Gap-134 prevented fibrosis despite the persistence of the conduction defects and the TGF-β canonical pathway activation[5]. Compared with placebo treatment dogs, oral GAP-134 dogs had a longer estimated LA wavelength (10.2+/-2.8 versus 8.0+/-1.4 cm, respectively, P<0.05). Oral GAP-134 did not significantly reduce AF inducibility or maintenance in the entire group of 24 placebo treatment dogs; in a subgroup of dogs (n=11) with less than 100% increase in LA systolic area, oral GAP-134 reduced AF induction from 100% to 40% and mean AF duration from 1737+/-120 to 615+/-280 seconds (P<0.05)[6]. Compared with the Middle Cerebral Artery Occlusion (MCAO) group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.43mL

0.69mL

0.34mL

17.16mL

3.43mL

1.72mL

34.33mL

6.87mL

3.43mL
参考文献

[1]De Vuyst E, Boengler K, et al. Pharmacological modulation of connexin-formed channels in cardiac pathophysiology. Br J Pharmacol. 2011 Jun;163(3):469-83.

[2]Hennan JK, Swillo RE, 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.

[3]Eric I Rossman,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]S Gigout,et al. Role of gap junctions on synchronization in human neocortical networks. Brain Res. 2016 Apr 15;1637:14-21.

[5]Justine Patin,et al. Gap-134, a Connexin43 activator, prevents age-related development of ventricular fibrosis in Scn5a +/- mice. Pharmacol Res. 2020 Sep;159:104922.

[6] Gabriel Laurent,et al. Effects of chronic gap junction conduction-enhancing antiarrhythmic peptide GAP-134 administration on experimental atrial fibrillation in dogs. Circ Arrhythm Electrophysiol. 2009 Apr;2(2):171-8.

[7] Kailing Yang,et al. Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134. Front Neurol. 2020 Aug 26;11:888.