Matches in SemOpenAlex for { <https://semopenalex.org/work/W2088835087> ?p ?o ?g. }
- W2088835087 endingPage "585" @default.
- W2088835087 startingPage "573" @default.
- W2088835087 abstract "Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Ligand efficiency was followed throughout our structure-activity studies. As applied within the context of LTA(4)H inhibitor design, the chemistry team was able to design a potent compound 20 (DG-051) (K(d) = 26 nM) with high aqueous solubility (>30 mg/mL) and high oral bioavailability (>80% across species) that is currently undergoing clinical evaluation for the treatment of myocardial infarction and stroke. The structural biology-chemistry interaction described in this paper provides a sound alternative to conventional screening techniques. This is the first example of a gene-to-clinic paradigm enabled by a fragment-based drug discovery effort." @default.
- W2088835087 created "2016-06-24" @default.
- W2088835087 creator A5000331239 @default.
- W2088835087 creator A5006521384 @default.
- W2088835087 creator A5017031485 @default.
- W2088835087 creator A5022438415 @default.
- W2088835087 creator A5023006896 @default.
- W2088835087 creator A5031480838 @default.
- W2088835087 creator A5036548817 @default.
- W2088835087 creator A5045145202 @default.
- W2088835087 creator A5047456350 @default.
- W2088835087 creator A5048874452 @default.
- W2088835087 creator A5049873352 @default.
- W2088835087 creator A5050073558 @default.
- W2088835087 creator A5051846333 @default.
- W2088835087 creator A5059724338 @default.
- W2088835087 creator A5062225186 @default.
- W2088835087 creator A5062481153 @default.
- W2088835087 creator A5070830358 @default.
- W2088835087 creator A5071672663 @default.
- W2088835087 creator A5074839520 @default.
- W2088835087 creator A5082265065 @default.
- W2088835087 creator A5085025902 @default.
- W2088835087 creator A5087327891 @default.
- W2088835087 creator A5087983188 @default.
- W2088835087 date "2009-12-01" @default.
- W2088835087 modified "2023-10-07" @default.
- W2088835087 title "Discovery of 4-[(2<i>S</i>)-2-{[4-(4-Chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic Acid (DG-051) as a Novel Leukotriene A4 Hydrolase Inhibitor of Leukotriene B4 Biosynthesis" @default.
- W2088835087 cites W1502177285 @default.
- W2088835087 cites W1858848970 @default.
- W2088835087 cites W186154380 @default.
- W2088835087 cites W1864533597 @default.
- W2088835087 cites W1968878164 @default.
- W2088835087 cites W1988409294 @default.
- W2088835087 cites W1988912265 @default.
- W2088835087 cites W1990044264 @default.
- W2088835087 cites W1992981307 @default.
- W2088835087 cites W1996100382 @default.
- W2088835087 cites W2001054421 @default.
- W2088835087 cites W2002758660 @default.
- W2088835087 cites W2008312146 @default.
- W2088835087 cites W2008525757 @default.
- W2088835087 cites W2009422790 @default.
- W2088835087 cites W2011677296 @default.
- W2088835087 cites W2012182437 @default.
- W2088835087 cites W2015261066 @default.
- W2088835087 cites W2025563699 @default.
- W2088835087 cites W2028767364 @default.
- W2088835087 cites W2028816469 @default.
- W2088835087 cites W2032255457 @default.
- W2088835087 cites W2033426097 @default.
- W2088835087 cites W2034510596 @default.
- W2088835087 cites W2045802827 @default.
- W2088835087 cites W2057241960 @default.
- W2088835087 cites W2059062943 @default.
- W2088835087 cites W2065432275 @default.
- W2088835087 cites W2085789404 @default.
- W2088835087 cites W2089533462 @default.
- W2088835087 cites W2089813764 @default.
- W2088835087 cites W2090908138 @default.
- W2088835087 cites W2092213963 @default.
- W2088835087 cites W2098532478 @default.
- W2088835087 cites W2100419832 @default.
- W2088835087 cites W2101700072 @default.
- W2088835087 cites W2106916053 @default.
- W2088835087 cites W2116430617 @default.
- W2088835087 cites W2130112063 @default.
- W2088835087 cites W2142184778 @default.
- W2088835087 cites W2145189353 @default.
- W2088835087 cites W2146807787 @default.
- W2088835087 cites W2147758955 @default.
- W2088835087 cites W2148365800 @default.
- W2088835087 cites W2154963167 @default.
- W2088835087 cites W2164400575 @default.
- W2088835087 cites W2166198189 @default.
- W2088835087 cites W233628489 @default.
- W2088835087 cites W2949625828 @default.
- W2088835087 cites W2953265736 @default.
- W2088835087 cites W4323915196 @default.
- W2088835087 doi "https://doi.org/10.1021/jm900838g" @default.
- W2088835087 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19950900" @default.
- W2088835087 hasPublicationYear "2009" @default.
- W2088835087 type Work @default.
- W2088835087 sameAs 2088835087 @default.
- W2088835087 citedByCount "57" @default.
- W2088835087 countsByYear W20888350872012 @default.
- W2088835087 countsByYear W20888350872013 @default.
- W2088835087 countsByYear W20888350872014 @default.
- W2088835087 countsByYear W20888350872015 @default.
- W2088835087 countsByYear W20888350872016 @default.
- W2088835087 countsByYear W20888350872017 @default.
- W2088835087 countsByYear W20888350872018 @default.
- W2088835087 countsByYear W20888350872019 @default.
- W2088835087 countsByYear W20888350872020 @default.
- W2088835087 countsByYear W20888350872021 @default.
- W2088835087 countsByYear W20888350872022 @default.
- W2088835087 countsByYear W20888350872023 @default.
- W2088835087 crossrefType "journal-article" @default.