ArticleCirculation research2009
Novel pharmacophores of connexin43 based on the "RXP" series of Cx43-binding peptides.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Connexin hemichannels as candidate targets for cardioprotective and anti-arrhythmic treatments.The Journal of clinical investigation · 2023Review
- Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine.Journal of cardiovascular development and disease · 2021Review
- Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke.The Journal of experimental medicine · 2019Article
- The SH3-binding domain of Cx43 participates in loop/tail interactions critical for Cx43-hemichannel activity.Cellular and molecular life sciences : CMLS · 2018Article
- Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.Pharmacological reviews · 2017Review
- Intramolecular signaling in a cardiac connexin: Role of cytoplasmic domain dimerization.Journal of molecular and cellular cardiology · 2017Article
- Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection.Pharmacology & therapeutics · 2015Review
- Cardiac to cancer: connecting connexins to clinical opportunity.FEBS letters · 2014Review
- Paracrine signaling through plasma membrane hemichannels.Biochimica et biophysica acta · 2013Review
- Manipulating connexin communication channels: use of peptidomimetics and the translational outputs.The Journal of membrane biology · 2012Review
- The connexin43 carboxyl terminus and cardiac gap junction organization.Biochimica et biophysica acta · 2012Review
- Gap junctions.Comprehensive Physiology · 2012Review
- Connexin43 and the regulation of intercalated disc function.Heart rhythm · 2012Article
- Novel molecular targets for atrial fibrillation therapy.Nature reviews. Drug discovery · 2012Review
- Glycogen synthase kinase 3β transfers cytoprotective signaling through connexin 43 onto mitochondrial ATP-sensitive K+ channels.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Pharmacological modulation of connexin-formed channels in cardiac pathophysiology.British journal of pharmacology · 2011Review
- Design and characterization of the first peptidomimetic molecule that prevents acidification-induced closure of cardiac gap junctions.Heart rhythm · 2010Article
- GJC2 missense mutations cause human lymphedema.American journal of human genetics · 2010Article
- Reduced expression of Cx43 attenuates ventricular remodeling after myocardial infarction via impaired TGF-beta signaling.American journal of physiology. Heart and circulatory physiology · 2010Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Gap junction pharmacology is a nascent field. Previous studies have identified molecules that enhance intercellular communication, and may offer potential for innovative antiarrhythmic therapy. However, their specific molecular target(s) and mechanism(s) of action remain unknown. Previously, we identified a 34-aa peptide (RXP-E) that binds the carboxyl terminal domain of Cx43 (Cx43CT) and prevents cardiac gap junction closure and action potential propagation block. These results supported the feasibility of a peptide-based pharmacology to Cx43, but the structure of the core active element in RXP-E, an essential step for pharmacological development, remained undefined. Here, we used a combination of molecular modeling, surface plasmon resonance, nuclear magnetic resonance and patch-clamp strategies to define, for the first time, a unique ensemble of pharmacophores that bind Cx43CT and prevent closure of Cx43 channels. Two particular molecules are best representatives of this family: a cyclized heptapeptide (called CyRP-71) and a linear octapeptide of sequence RRNYRRNY. These 2 small compounds offer the first structural platform for the design of Cx43-interacting gap junction openers. Moreover, the structure of these compounds offers an imprint of a region of Cx43CT that is fundamental to gap junction channel function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.