Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912171584> ?p ?o ?g. }
- W2912171584 endingPage "229" @default.
- W2912171584 startingPage "224" @default.
- W2912171584 abstract "Despite intense interest in expanding chemical space, libraries containing hundreds-of-millions to billions of diverse molecules have remained inaccessible. Here we investigate structure-based docking of 170 million make-on-demand compounds from 130 well-characterized reactions. The resulting library is diverse, representing over 10.7 million scaffolds that are otherwise unavailable. For each compound in the library, docking against AmpC β-lactamase (AmpC) and the D4 dopamine receptor were simulated. From the top-ranking molecules, 44 and 549 compounds were synthesized and tested for interactions with AmpC and the D4 dopamine receptor, respectively. We found a phenolate inhibitor of AmpC, which revealed a group of inhibitors without known precedent. This molecule was optimized to 77 nM, which places it among the most potent non-covalent AmpC inhibitors known. Crystal structures of this and other AmpC inhibitors confirmed the docking predictions. Against the D4 dopamine receptor, hit rates fell almost monotonically with docking score, and a hit-rate versus score curve predicted that the library contained 453,000 ligands for the D4 dopamine receptor. Of 81 new chemotypes discovered, 30 showed submicromolar activity, including a 180-pM subtype-selective agonist of the D4 dopamine receptor." @default.
- W2912171584 created "2019-02-21" @default.
- W2912171584 creator A5002654936 @default.
- W2912171584 creator A5005823028 @default.
- W2912171584 creator A5006999859 @default.
- W2912171584 creator A5007856961 @default.
- W2912171584 creator A5008941924 @default.
- W2912171584 creator A5009419179 @default.
- W2912171584 creator A5013356903 @default.
- W2912171584 creator A5033111996 @default.
- W2912171584 creator A5041554247 @default.
- W2912171584 creator A5044952613 @default.
- W2912171584 creator A5051549888 @default.
- W2912171584 creator A5054045417 @default.
- W2912171584 creator A5074902300 @default.
- W2912171584 creator A5091597046 @default.
- W2912171584 date "2019-02-01" @default.
- W2912171584 modified "2023-10-16" @default.
- W2912171584 title "Ultra-large library docking for discovering new chemotypes" @default.
- W2912171584 cites W1174108660 @default.
- W2912171584 cites W1757990252 @default.
- W2912171584 cites W1968319881 @default.
- W2912171584 cites W1970658820 @default.
- W2912171584 cites W1976975058 @default.
- W2912171584 cites W1978009405 @default.
- W2912171584 cites W1980285986 @default.
- W2912171584 cites W1984030577 @default.
- W2912171584 cites W1984384096 @default.
- W2912171584 cites W1990627326 @default.
- W2912171584 cites W2000350990 @default.
- W2912171584 cites W2003194288 @default.
- W2912171584 cites W2007980582 @default.
- W2912171584 cites W2009423060 @default.
- W2912171584 cites W2013578231 @default.
- W2912171584 cites W2017254234 @default.
- W2912171584 cites W2017423606 @default.
- W2912171584 cites W2020389339 @default.
- W2912171584 cites W2020577176 @default.
- W2912171584 cites W2021580832 @default.
- W2912171584 cites W2025948031 @default.
- W2912171584 cites W2026501736 @default.
- W2912171584 cites W2029087609 @default.
- W2912171584 cites W2031903144 @default.
- W2912171584 cites W2038617772 @default.
- W2912171584 cites W2038840577 @default.
- W2912171584 cites W2039384791 @default.
- W2912171584 cites W2043209972 @default.
- W2912171584 cites W2044157091 @default.
- W2912171584 cites W2047473926 @default.
- W2912171584 cites W2050273205 @default.
- W2912171584 cites W2050456292 @default.
- W2912171584 cites W2058835307 @default.
- W2912171584 cites W2060531713 @default.
- W2912171584 cites W2061583504 @default.
- W2912171584 cites W2077627456 @default.
- W2912171584 cites W2078374001 @default.
- W2912171584 cites W2079159737 @default.
- W2912171584 cites W2082956345 @default.
- W2912171584 cites W2094208194 @default.
- W2912171584 cites W2101484286 @default.
- W2912171584 cites W2103300124 @default.
- W2912171584 cites W2112894447 @default.
- W2912171584 cites W2114411231 @default.
- W2912171584 cites W2124026197 @default.
- W2912171584 cites W2127287358 @default.
- W2912171584 cites W2128581376 @default.
- W2912171584 cites W2142182637 @default.
- W2912171584 cites W2143216536 @default.
- W2912171584 cites W2145487150 @default.
- W2912171584 cites W2159266419 @default.
- W2912171584 cites W2166478947 @default.
- W2912171584 cites W2171234651 @default.
- W2912171584 cites W2176349682 @default.
- W2912171584 cites W2180229411 @default.
- W2912171584 cites W2274656763 @default.
- W2912171584 cites W2324869514 @default.
- W2912171584 cites W2471437780 @default.
- W2912171584 cites W2473421018 @default.
- W2912171584 cites W2510692111 @default.
- W2912171584 cites W2512819857 @default.
- W2912171584 cites W2558999090 @default.
- W2912171584 cites W2560677837 @default.
- W2912171584 cites W2577537660 @default.
- W2912171584 cites W2580819390 @default.
- W2912171584 cites W2613490892 @default.
- W2912171584 cites W2766694609 @default.
- W2912171584 cites W2769567666 @default.
- W2912171584 cites W2805951153 @default.
- W2912171584 cites W2982809992 @default.
- W2912171584 cites W4248872320 @default.
- W2912171584 doi "https://doi.org/10.1038/s41586-019-0917-9" @default.
- W2912171584 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6383769" @default.
- W2912171584 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30728502" @default.
- W2912171584 hasPublicationYear "2019" @default.
- W2912171584 type Work @default.
- W2912171584 sameAs 2912171584 @default.
- W2912171584 citedByCount "513" @default.
- W2912171584 countsByYear W29121715842019 @default.