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Structure–Activity Relationship Studies of Functionally Selective Kappa Opioid Receptor Agonists that Modulate ERK 1/2 Phosphorylation While Preserving G Protein Over βArrestin2 Signaling Bias
dc.contributor.author | Lovell, Kimberly M. | |
dc.contributor.author | Frankowski, Kevin J. | |
dc.contributor.author | Stahl, Edward L. | |
dc.contributor.author | Slauson, Stephen R. | |
dc.contributor.author | Yoo, Euna | |
dc.contributor.author | Prisinzano, Thomas E. | |
dc.contributor.author | Aubé, Jeffrey | |
dc.contributor.author | Bohn, Laura M. | |
dc.date.accessioned | 2017-04-27T18:09:51Z | |
dc.date.available | 2017-04-27T18:09:51Z | |
dc.date.issued | 2015-08-19 | |
dc.identifier.citation | Lovell, K. M., Frankowski, K. J., Stahl, E. L., Slauson, S. R., Yoo, E., Prisinzano, T. E., … Bohn, L. M. (2015). Structure–Activity Relationship Studies of Functionally Selective Kappa Opioid Receptor Agonists that Modulate ERK 1/2 Phosphorylation While Preserving G Protein Over βArrestin2 Signaling Bias. ACS Chemical Neuroscience, 6(8), 1411–1419. http://doi.org/10.1021/acschemneuro.5b00092 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23838 | |
dc.description.abstract | Kappa opioid receptor (KOR) modulation is a promising target for drug discovery efforts due to KOR involvement in pain, depression, and addiction behaviors. We recently reported a new class of triazole KOR agonists that displays significant bias toward G protein signaling over βarrestin2 recruitment; interestingly, these compounds also induce less activation of ERK1/2 map kinases than the balanced agonist, U69,593. We have identified structure–activity relationships around the triazole scaffold that allows for decreasing the bias for G protein signaling over ERK1/2 activation while maintaining the bias for G protein signaling over βarrestin2 recruitment. The development of novel compounds, with different downstream signaling outcomes, independent of G protein/βarrestin2 bias, provides a more diverse pharmacological toolset for use in defining complex KOR signaling and elucidating the significance of KOR-mediated signaling. | en_US |
dc.publisher | ACS | en_US |
dc.rights | Copyright © 2015 American Chemical Society | en_US |
dc.subject | Functional selectivity | en_US |
dc.subject | MAP kinase | en_US |
dc.subject | Biased agonism | en_US |
dc.subject | G protein coupling | en_US |
dc.subject | Arrestin | en_US |
dc.subject | GPCR | en_US |
dc.title | Structure–Activity Relationship Studies of Functionally Selective Kappa Opioid Receptor Agonists that Modulate ERK 1/2 Phosphorylation While Preserving G Protein Over βArrestin2 Signaling Bias | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Frankowski, Kevin J. | |
kusw.kuauthor | Slauson, Stephen R. | |
kusw.kuauthor | Yoo, Euna | |
kusw.kuauthor | Prisinzano, Thomas E. | |
kusw.kuauthor | Aubé, Jeffrey | |
kusw.kudepartment | Medicinal Chemistry | en_US |
dc.identifier.doi | 10.1021/acschemneuro.5b00092 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-1049-5767 https://orcid.org/0000-0002-2811-2894 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4830356 | en_US |
dc.rights.accessrights | openAccess |