Matches in SemOpenAlex for { <https://semopenalex.org/work/W2801012012> ?p ?o ?g. }
- W2801012012 endingPage "154" @default.
- W2801012012 startingPage "145" @default.
- W2801012012 abstract "α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the ‘racemisation’ reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure–activity relationship study has been performed. This paper describes the first structure–activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC50 = 400–750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure–activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation." @default.
- W2801012012 created "2018-05-17" @default.
- W2801012012 creator A5012784466 @default.
- W2801012012 creator A5016634968 @default.
- W2801012012 creator A5024872462 @default.
- W2801012012 creator A5036024913 @default.
- W2801012012 creator A5044872143 @default.
- W2801012012 creator A5061465946 @default.
- W2801012012 creator A5062116698 @default.
- W2801012012 creator A5070852723 @default.
- W2801012012 date "2018-09-01" @default.
- W2801012012 modified "2023-10-16" @default.
- W2801012012 title "Structure-activity relationships of rationally designed AMACR 1A inhibitors" @default.
- W2801012012 cites W1496079625 @default.
- W2801012012 cites W1872235201 @default.
- W2801012012 cites W1963762892 @default.
- W2801012012 cites W1964319629 @default.
- W2801012012 cites W1966056172 @default.
- W2801012012 cites W1987684836 @default.
- W2801012012 cites W1991052542 @default.
- W2801012012 cites W1995188759 @default.
- W2801012012 cites W1995527507 @default.
- W2801012012 cites W1998884175 @default.
- W2801012012 cites W2002076420 @default.
- W2801012012 cites W2007852631 @default.
- W2801012012 cites W2012810767 @default.
- W2801012012 cites W2022904488 @default.
- W2801012012 cites W2024400005 @default.
- W2801012012 cites W2029376999 @default.
- W2801012012 cites W2034664043 @default.
- W2801012012 cites W2036033631 @default.
- W2801012012 cites W2054981343 @default.
- W2801012012 cites W2057531529 @default.
- W2801012012 cites W2060768796 @default.
- W2801012012 cites W2066224900 @default.
- W2801012012 cites W2078927874 @default.
- W2801012012 cites W2101448730 @default.
- W2801012012 cites W2108016495 @default.
- W2801012012 cites W2110188341 @default.
- W2801012012 cites W2115920211 @default.
- W2801012012 cites W2131819439 @default.
- W2801012012 cites W2131992364 @default.
- W2801012012 cites W2139144280 @default.
- W2801012012 cites W2139154860 @default.
- W2801012012 cites W2148881880 @default.
- W2801012012 cites W2149818368 @default.
- W2801012012 cites W2170960986 @default.
- W2801012012 cites W2198737390 @default.
- W2801012012 cites W2262693112 @default.
- W2801012012 cites W2327716564 @default.
- W2801012012 cites W2596319814 @default.
- W2801012012 cites W2791664580 @default.
- W2801012012 cites W2953280961 @default.
- W2801012012 cites W4243267307 @default.
- W2801012012 doi "https://doi.org/10.1016/j.bioorg.2018.04.024" @default.
- W2801012012 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29751320" @default.
- W2801012012 hasPublicationYear "2018" @default.
- W2801012012 type Work @default.
- W2801012012 sameAs 2801012012 @default.
- W2801012012 citedByCount "7" @default.
- W2801012012 countsByYear W28010120122019 @default.
- W2801012012 countsByYear W28010120122020 @default.
- W2801012012 countsByYear W28010120122021 @default.
- W2801012012 countsByYear W28010120122023 @default.
- W2801012012 crossrefType "journal-article" @default.
- W2801012012 hasAuthorship W2801012012A5012784466 @default.
- W2801012012 hasAuthorship W2801012012A5016634968 @default.
- W2801012012 hasAuthorship W2801012012A5024872462 @default.
- W2801012012 hasAuthorship W2801012012A5036024913 @default.
- W2801012012 hasAuthorship W2801012012A5044872143 @default.
- W2801012012 hasAuthorship W2801012012A5061465946 @default.
- W2801012012 hasAuthorship W2801012012A5062116698 @default.
- W2801012012 hasAuthorship W2801012012A5070852723 @default.
- W2801012012 hasBestOaLocation W28010120122 @default.
- W2801012012 hasConcept C171250308 @default.
- W2801012012 hasConcept C181199279 @default.
- W2801012012 hasConcept C185592680 @default.
- W2801012012 hasConcept C192562407 @default.
- W2801012012 hasConcept C193042331 @default.
- W2801012012 hasConcept C201399114 @default.
- W2801012012 hasConcept C202751555 @default.
- W2801012012 hasConcept C2776980637 @default.
- W2801012012 hasConcept C2777752497 @default.
- W2801012012 hasConcept C2780035454 @default.
- W2801012012 hasConcept C2989108626 @default.
- W2801012012 hasConcept C53105671 @default.
- W2801012012 hasConcept C55493867 @default.
- W2801012012 hasConcept C57992300 @default.
- W2801012012 hasConcept C71240020 @default.
- W2801012012 hasConcept C71924100 @default.
- W2801012012 hasConcept C98274493 @default.
- W2801012012 hasConceptScore W2801012012C171250308 @default.
- W2801012012 hasConceptScore W2801012012C181199279 @default.
- W2801012012 hasConceptScore W2801012012C185592680 @default.
- W2801012012 hasConceptScore W2801012012C192562407 @default.
- W2801012012 hasConceptScore W2801012012C193042331 @default.
- W2801012012 hasConceptScore W2801012012C201399114 @default.
- W2801012012 hasConceptScore W2801012012C202751555 @default.