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

2009 ◽  
Vol 52 (4) ◽  
pp. 908-911 ◽  
Author(s):  
John A. Butera ◽  
Bjarne Due Larsen ◽  
James K. Hennan ◽  
Edward Kerns ◽  
Li Di ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Carboxylic Acid ◽  
Gap Junction ◽  
Small Molecule ◽  
Acid Hydrochloride ◽  
Orally Active

The role of angiotensin in electrophysiological gap junction remodeling in human atrial fibrillation

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
S Dhein ◽  
A Boldt ◽  
J Garbade ◽  
L Polontchouk ◽  
U Wetzel ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Human Atrial Fibrillation

GSK-3 inhibition by an orally active small molecule increases bone mass in rats

Bone ◽  
2012 ◽  
Vol 50 (3) ◽  
pp. 619-627 ◽  
Author(s):  
Richard Marsell ◽  
Gregor Sisask ◽  
Yvonne Nilsson ◽  
Anna K. Sundgren-Andersson ◽  
Ulf Andersson ◽  
...  
Keyword(s):  
Bone Mass ◽  
Small Molecule ◽  
Orally Active

Increasing membrane permeability of carboxylic acid-containing drugs using synthetic transmembrane anion transporters

2021 ◽  
Author(s):  
Rayhanus Salam ◽  
Surid Mohammad Chowdhury ◽  
Sarah Ruth Marshall ◽  
Hassan Gneid ◽  
Nathalie Busschaert
Keyword(s):  
Carboxylic Acid ◽  
Membrane Permeability ◽  
Lipid Bilayers ◽  
Small Molecule ◽  
Anion Transporters

In this manuscript, we show that small-molecule-based anion transporters can significantly increase the permeability of carboxylic acid containing drugs across lipid bilayers of model vesicles. Due to the drug-like characteristics...

Abstract 1087: Effects of Oral Gap Junction Conduction-Enhancing Antiarrhythmic Peptide GAP-134 on Experimental Atrial Fibrillation in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gabriel Laurent ◽  
Howard Leong-Poi ◽  
Gordon Moe ◽  
Xudong Hu ◽  
Petsy Pui-Sze So ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Electrophysiological Study ◽  
Placebo Treatment ◽  
Refractory Periods ◽  
Percent Change ◽  
Dog Model ◽  
Antiarrhythmic Peptide ◽  
The Mean ◽  
Mechanical Remodeling

Background: Abnormal intercellular communication caused by connexin dysfunction may promote atrial fibrillation (AF). Objective: To assess the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a new dog model of atrial cardiomyopathy. Methods and Results: Twenty four dogs underwent simultaneous atrioventricular pacing (2 weeks at 220 bpm, atrioventricular delay 0 ms), and were randomly assigned to placebo treatment (PACED-PLACEBO; 12 dogs) or oral GAP-134 (PACED-GAP 134; 12 dogs) (starting at day 0). Percent change in left atrial systolic area (Δ% LASA) from baseline to 2 weeks was calculated using trans-esophageal echocardiography. At 2 weeks, animals underwent an open chest electrophysiological study; conduction velocity (CV) when pacing at 150ms cycle length (CL), effective refractory periods (ERP) and AF vulnerability were measured. The mean plasma concentration of GAP-134 was 557 ± 239 nmol/L. GAP-134 increased CV (395.1 ± 63.2 vs 307.8 ± 54.6 mm/s, p<0.01), and shortened ERP at 200ms CL (104.0 ± 8.6 vs 112.8 ± 11.5 ms, P<0.05). GAP-134 significantly reduced AF inducibility [% burst attempts inducing AF] and maintenance [mean AF duration, number of episodes >10min] in dogs with less than 100% ΔLASA (n=5). In dogs with more structural remodeling (ΔLASA ≥100%, n=7), CV increased but AF inducibility was unaffected. Conclusions: Oral GAP-134 prevents CV slowing in a dog model of atrial cardiomyopathy, but attenuates AF inducibility and maintenance only in dogs with less mechanical remodeling.

Metformin therapy confers cardioprotection against the remodeling of gap junction in tachycardia-induced atrial fibrillation dog model

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 117759 ◽  
Author(s):  
Jiayi Li ◽  
Biao Li ◽  
Fan Bai ◽  
Yinxu Ma ◽  
Na Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Metformin Therapy ◽  
Dog Model

P2-481: Small molecule BACE-1 inhibitors are potent, selective and orally active

2008 ◽  
Vol 4 ◽  
pp. T515-T515
Author(s):  
Michael Malamas ◽  
Jim Erdei ◽  
Iwan Gunawan ◽  
Albert Robichaud ◽  
Jim Turner ◽  
...  
Keyword(s):  
Small Molecule ◽  
Orally Active ◽  
Bace 1

scholarly journals Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists

2016 ◽  
Vol 26 (5) ◽  
pp. 1480-1484 ◽  
Author(s):  
Lori A. Emert-Sedlak ◽  
H. Marie Loughran ◽  
Haibin Shi ◽  
John L. Kulp ◽  
Sherry T. Shu ◽  
...  
Keyword(s):  
Small Molecule ◽  
Orally Active ◽  
Hiv 1
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