FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2790759849> ?p ?o ?g. }

• W2790759849 endingPage "591" @default.
• W2790759849 startingPage "581" @default.
• W2790759849 abstract "GPR40 is a clinically validated molecular target for the treatment of diabetes. Many GPR40 agonists have been identified to date, with the partial agonist fasiglifam (TAK-875) reaching phase III clinical trials before its development was terminated due to off-target liver toxicity. Since then, attention has shifted toward the development of full agonists that exhibit superior efficacy in preclinical models. Full agonists bind to a distinct binding site, suggesting conformational plasticity and a potential for biased agonism. Indeed, it has been suggested that alternative pharmacology may be required for meaningful efficacy. In this study, we described the discovery and characterization of Compound A, a newly identified GPR40 allosteric full agonist highly efficacious in human islets at potentiating glucose-stimulated insulin secretion. We compared Compound A–induced GPR40 activity to that induced by both fasiglifam and AM-1638, another allosteric full agonist previously reported to be highly efficacious in preclinical models, at a panel of G proteins. Compound A was a full agonist at both the G<i>α</i>q and G<i>α</i>i2 pathways, and in contrast to fasiglifam Compound A also induced G<i>α</i>12 coupling. Compound A and AM-1638 displayed similar activity at all pathways tested. The G<i>α</i>₁₂/G<i>α</i>₁₃-mediated signaling pathway has been linked to protein kinase D activation as well as actin remodeling, well known to contribute to the release of insulin vesicles. Our data suggest that the pharmacology of GPR40 is complex and that G<i>α</i>12/G<i>α</i>13-mediated signaling, which may contribute to GPR40 agonists therapeutic efficacy, is a specific property of GPR40 allosteric full agonists." @default.
• W2790759849 created "2018-03-29" @default.
• W2790759849 creator A5001684173 @default.
• W2790759849 creator A5021687135 @default.
• W2790759849 creator A5021853876 @default.
• W2790759849 creator A5022322678 @default.
• W2790759849 creator A5040533601 @default.
• W2790759849 creator A5042693068 @default.
• W2790759849 creator A5042762022 @default.
• W2790759849 creator A5043040392 @default.
• W2790759849 creator A5058953422 @default.
• W2790759849 creator A5072762516 @default.
• W2790759849 creator A5073365115 @default.
• W2790759849 creator A5077713732 @default.
• W2790759849 date "2018-03-23" @default.
• W2790759849 modified "2023-09-27" @default.
• W2790759849 title "GPR40-Mediated G<i>α</i>12 Activation by Allosteric Full Agonists Highly Efficacious at Potentiating Glucose-Stimulated Insulin Secretion in Human Islets" @default.
• W2790759849 cites W1193047888 @default.
• W2790759849 cites W138314167 @default.
• W2790759849 cites W1857361913 @default.
• W2790759849 cites W1964225232 @default.
• W2790759849 cites W1968817307 @default.
• W2790759849 cites W1971557502 @default.
• W2790759849 cites W1973433839 @default.
• W2790759849 cites W1974405795 @default.
• W2790759849 cites W1979161189 @default.
• W2790759849 cites W1993139191 @default.
• W2790759849 cites W1995613581 @default.
• W2790759849 cites W1999927420 @default.
• W2790759849 cites W2006803138 @default.
• W2790759849 cites W2010099293 @default.
• W2790759849 cites W2010347555 @default.
• W2790759849 cites W2025703258 @default.
• W2790759849 cites W2026568039 @default.
• W2790759849 cites W2042311529 @default.
• W2790759849 cites W2043606482 @default.
• W2790759849 cites W2048495619 @default.
• W2790759849 cites W2061422418 @default.
• W2790759849 cites W2075009646 @default.
• W2790759849 cites W2077936393 @default.
• W2790759849 cites W2079159737 @default.
• W2790759849 cites W2080410583 @default.
• W2790759849 cites W2084948079 @default.
• W2790759849 cites W2089540591 @default.
• W2790759849 cites W2096229924 @default.
• W2790759849 cites W2102944287 @default.
• W2790759849 cites W2102964449 @default.
• W2790759849 cites W2106036385 @default.
• W2790759849 cites W2109967142 @default.
• W2790759849 cites W2115276803 @default.
• W2790759849 cites W2119446720 @default.
• W2790759849 cites W2126988283 @default.
• W2790759849 cites W2128326754 @default.
• W2790759849 cites W2141641107 @default.
• W2790759849 cites W2148829653 @default.
• W2790759849 cites W2150854800 @default.
• W2790759849 cites W2163448046 @default.
• W2790759849 cites W2167857702 @default.
• W2790759849 cites W2191622804 @default.
• W2790759849 cites W2281241032 @default.
• W2790759849 cites W2346521219 @default.
• W2790759849 cites W2366624464 @default.
• W2790759849 cites W2469309996 @default.
• W2790759849 cites W2519198844 @default.
• W2790759849 cites W2558012631 @default.
• W2790759849 cites W2582287106 @default.
• W2790759849 cites W2587893840 @default.
• W2790759849 cites W2597253785 @default.
• W2790759849 cites W2622916369 @default.
• W2790759849 doi "https://doi.org/10.1124/mol.117.111369" @default.
• W2790759849 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29572336" @default.
• W2790759849 hasPublicationYear "2018" @default.
• W2790759849 type Work @default.
• W2790759849 sameAs 2790759849 @default.
• W2790759849 citedByCount "19" @default.
• W2790759849 countsByYear W27907598492019 @default.
• W2790759849 countsByYear W27907598492020 @default.
• W2790759849 countsByYear W27907598492021 @default.
• W2790759849 countsByYear W27907598492022 @default.
• W2790759849 countsByYear W27907598492023 @default.
• W2790759849 crossrefType "journal-article" @default.
• W2790759849 hasAuthorship W2790759849A5001684173 @default.
• W2790759849 hasAuthorship W2790759849A5021687135 @default.
• W2790759849 hasAuthorship W2790759849A5021853876 @default.
• W2790759849 hasAuthorship W2790759849A5022322678 @default.
• W2790759849 hasAuthorship W2790759849A5040533601 @default.
• W2790759849 hasAuthorship W2790759849A5042693068 @default.
• W2790759849 hasAuthorship W2790759849A5042762022 @default.
• W2790759849 hasAuthorship W2790759849A5043040392 @default.
• W2790759849 hasAuthorship W2790759849A5058953422 @default.
• W2790759849 hasAuthorship W2790759849A5072762516 @default.
• W2790759849 hasAuthorship W2790759849A5073365115 @default.
• W2790759849 hasAuthorship W2790759849A5077713732 @default.
• W2790759849 hasBestOaLocation W27907598491 @default.
• W2790759849 hasConcept C134018914 @default.
• W2790759849 hasConcept C135285700 @default.
• W2790759849 hasConcept C166342909 @default.
• W2790759849 hasConcept C170493617 @default.

• next