The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation
AbstractThe 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. View Full-Text
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Barker, G.; Parnell, E.; Van Basten, B.; Buist, H.; Adams, D.R.; Yarwood, S.J. The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation. J. Cardiovasc. Dev. Dis. 2017, 4, 22.
Barker G, Parnell E, Van Basten B, Buist H, Adams DR, Yarwood SJ. The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation. Journal of Cardiovascular Development and Disease. 2017; 4(4):22.Chicago/Turabian Style
Barker, Graeme; Parnell, Euan; Van Basten, Boy; Buist, Hanna; Adams, David R.; Yarwood, Stephen J. 2017. "The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation." J. Cardiovasc. Dev. Dis. 4, no. 4: 22.
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