The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation
| Autor: | Stephen J. Yarwood, Boy van Basten, David R. Adams, Graeme Barker, Hanna K. Buist, Euan Parnell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist lcsh:Diseases of the circulatory (Cardiovascular) system medicine.drug_class EPAC1 Inflammation Review Suppressor of cytokine signalling high-throughput screening Proinflammatory cytokine 03 medical and health sciences medicine Pharmacology (medical) cyclic AMP SOCS3 General Pharmacology Toxicology and Pharmaceutics business.industry Activator (genetics) endothelial cells 030104 developmental biology Signalling Proteasome lcsh:RC666-701 inflammation cyclic nucleotide binding domain Cancer research medicine.symptom business |
| Zdroj: | Journal of Cardiovascular Development and Disease Journal of Cardiovascular Development and Disease, Vol 4, Iss 4, p 22 (2017) |
| ISSN: | 2308-3425 |
| Popis: | The cyclic 3′,5′-adenosine monophosphate (cAMP) sensor enzyme, EPAC1, is a candidate drug target in vascular endothelial cells (VECs) due to its ability to attenuate proinflammatory cytokine signalling normally associated with cardiovascular diseases (CVDs), including atherosclerosis. This is through the EPAC1-dependent induction of the suppressor of cytokine signalling gene, SOCS3, which targets inflammatory signalling proteins for ubiquitinylation and destruction by the proteosome. Given this important role for the EPAC1/SOCS3 signalling axis, we have used high throughput screening (HTS) to identify small molecule EPAC1 regulators and have recently isolated the first known non-cyclic nucleotide (NCN) EPAC1 agonist, I942. I942 therefore represents the first in class, isoform selective EPAC1 activator, with the potential to suppress pro-inflammatory cytokine signalling with a reduced risk of side effects associated with general cAMP-elevating agents that activate multiple response pathways. The development of augmented I942 analogues may therefore provide improved research tools to validate EPAC1 as a potential therapeutic target for the treatment of chronic inflammation associated with deadly CVDs. |
| Databáze: | OpenAIRE |
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