Matches in SemOpenAlex for { <https://semopenalex.org/work/W1505662983> ?p ?o ?g. }
- W1505662983 endingPage "1061" @default.
- W1505662983 startingPage "1054" @default.
- W1505662983 abstract "The alpha7 nicotinic acetylcholine receptor (nAChR) has attracted considerable interest as a target for cognitive enhancement in schizophrenia and Alzheimer's Disease. However, most recently described alpha7 agonists are derived from the quinuclidine structural class. Alternatively, the present study identifies tilorone as a novel alpha7-selective agonist and characterizes analogues developed from this lead.Activity and selectivity were determined from rat brain alpha7 and alpha4beta2 nAChR binding, recombinant nAChR activation, and native alpha7 nAChR mediated stimulation of ERK1/2 phosphorylation in PC12 cells.Tilorone bound alpha7 nAChR (IC(50) 110 nM) with high selectivity relative to alpha4beta2 (IC(50) 70 000 nM), activated human alpha7 nAChR with an EC(50) value of 2.5 microM and maximal response of 67% relative to acetylcholine, and showed little agonist effect at human alpha3beta4 or alpha4beta2 nAChRs. However, the rat alpha7 nAChR maximal response was only 34%. Lead optimization led to 2-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-xanthen-9-one (A-844606) with improved binding (alpha7 IC(50) 11 nM, alpha4beta2 IC(50)>30 000 nM) and activity at both human and rat alpha7 nAChR (EC(50)s 1.4 and 2.2 microM and apparent efficacies 61 and 63%, respectively). These compounds also activated native alpha7 nAChR, stimulating ERK1/2 phosphorylation in PC12 cells.Tilorone, known as an interferon inducer, is a selective alpha7 nAChR agonist, suggesting utility of the fluorenone pharmacophore for the development of alpha7 nAChR selective agonists. Whether alpha7 stimulation mediates interferon induction, or whether interferon induction may influence the potential anti-inflammatory properties of alpha7 nAChR agonists remains to be elucidated." @default.
- W1505662983 created "2016-06-24" @default.
- W1505662983 creator A5009915748 @default.
- W1505662983 creator A5013364999 @default.
- W1505662983 creator A5015846952 @default.
- W1505662983 creator A5018994264 @default.
- W1505662983 creator A5027440780 @default.
- W1505662983 creator A5036241946 @default.
- W1505662983 creator A5044940190 @default.
- W1505662983 creator A5063250449 @default.
- W1505662983 creator A5065694451 @default.
- W1505662983 creator A5073315335 @default.
- W1505662983 creator A5073992167 @default.
- W1505662983 creator A5075581321 @default.
- W1505662983 creator A5085194798 @default.
- W1505662983 date "2008-03-01" @default.
- W1505662983 modified "2023-09-27" @default.
- W1505662983 title "α7 nicotinic acetylcholine receptor agonist properties of tilorone and related tricyclic analogues" @default.
- W1505662983 cites W129138400 @default.
- W1505662983 cites W1493574533 @default.
- W1505662983 cites W1547160898 @default.
- W1505662983 cites W1859480879 @default.
- W1505662983 cites W1963656077 @default.
- W1505662983 cites W1964072039 @default.
- W1505662983 cites W1974100135 @default.
- W1505662983 cites W1974306203 @default.
- W1505662983 cites W1978071150 @default.
- W1505662983 cites W1984983082 @default.
- W1505662983 cites W1986101280 @default.
- W1505662983 cites W1993337719 @default.
- W1505662983 cites W1993373360 @default.
- W1505662983 cites W1994478897 @default.
- W1505662983 cites W1994910390 @default.
- W1505662983 cites W1995846564 @default.
- W1505662983 cites W2005044038 @default.
- W1505662983 cites W2009823032 @default.
- W1505662983 cites W2016729909 @default.
- W1505662983 cites W2024114406 @default.
- W1505662983 cites W2032206588 @default.
- W1505662983 cites W2046437271 @default.
- W1505662983 cites W2048439122 @default.
- W1505662983 cites W2051876547 @default.
- W1505662983 cites W2052861568 @default.
- W1505662983 cites W2056981505 @default.
- W1505662983 cites W2057196462 @default.
- W1505662983 cites W2072018779 @default.
- W1505662983 cites W2073977687 @default.
- W1505662983 cites W2074915076 @default.
- W1505662983 cites W2075791764 @default.
- W1505662983 cites W2081686317 @default.
- W1505662983 cites W2085263815 @default.
- W1505662983 cites W2086246203 @default.
- W1505662983 cites W2093671206 @default.
- W1505662983 cites W2116043647 @default.
- W1505662983 cites W2120349084 @default.
- W1505662983 cites W2124533302 @default.
- W1505662983 cites W2125651649 @default.
- W1505662983 cites W2126618993 @default.
- W1505662983 cites W2140445474 @default.
- W1505662983 cites W2145593805 @default.
- W1505662983 cites W2146608786 @default.
- W1505662983 cites W2146710322 @default.
- W1505662983 cites W2152473396 @default.
- W1505662983 cites W2156076504 @default.
- W1505662983 cites W2162845180 @default.
- W1505662983 cites W2165864165 @default.
- W1505662983 cites W2338521704 @default.
- W1505662983 cites W2951178485 @default.
- W1505662983 cites W4253430828 @default.
- W1505662983 cites W4255450278 @default.
- W1505662983 cites W878607483 @default.
- W1505662983 doi "https://doi.org/10.1038/sj.bjp.0707649" @default.
- W1505662983 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2267268" @default.
- W1505662983 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18157163" @default.
- W1505662983 hasPublicationYear "2008" @default.
- W1505662983 type Work @default.
- W1505662983 sameAs 1505662983 @default.
- W1505662983 citedByCount "36" @default.
- W1505662983 countsByYear W15056629832012 @default.
- W1505662983 countsByYear W15056629832013 @default.
- W1505662983 countsByYear W15056629832014 @default.
- W1505662983 countsByYear W15056629832015 @default.
- W1505662983 countsByYear W15056629832016 @default.
- W1505662983 countsByYear W15056629832017 @default.
- W1505662983 countsByYear W15056629832018 @default.
- W1505662983 countsByYear W15056629832020 @default.
- W1505662983 countsByYear W15056629832021 @default.
- W1505662983 crossrefType "journal-article" @default.
- W1505662983 hasAuthorship W1505662983A5009915748 @default.
- W1505662983 hasAuthorship W1505662983A5013364999 @default.
- W1505662983 hasAuthorship W1505662983A5015846952 @default.
- W1505662983 hasAuthorship W1505662983A5018994264 @default.
- W1505662983 hasAuthorship W1505662983A5027440780 @default.
- W1505662983 hasAuthorship W1505662983A5036241946 @default.
- W1505662983 hasAuthorship W1505662983A5044940190 @default.
- W1505662983 hasAuthorship W1505662983A5063250449 @default.
- W1505662983 hasAuthorship W1505662983A5065694451 @default.
- W1505662983 hasAuthorship W1505662983A5073315335 @default.