Matches in SemOpenAlex for { <https://semopenalex.org/work/W2562585861> ?p ?o ?g. }
- W2562585861 endingPage "1125" @default.
- W2562585861 startingPage "1105" @default.
- W2562585861 abstract "Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule 20 (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with human GlyRα3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs)." @default.
- W2562585861 created "2017-01-06" @default.
- W2562585861 creator A5006698956 @default.
- W2562585861 creator A5007100513 @default.
- W2562585861 creator A5008080434 @default.
- W2562585861 creator A5009300129 @default.
- W2562585861 creator A5009651273 @default.
- W2562585861 creator A5011428138 @default.
- W2562585861 creator A5022466041 @default.
- W2562585861 creator A5022499603 @default.
- W2562585861 creator A5027760014 @default.
- W2562585861 creator A5028265641 @default.
- W2562585861 creator A5032337429 @default.
- W2562585861 creator A5032342352 @default.
- W2562585861 creator A5034056485 @default.
- W2562585861 creator A5037496059 @default.
- W2562585861 creator A5044962386 @default.
- W2562585861 creator A5049963165 @default.
- W2562585861 creator A5051379817 @default.
- W2562585861 creator A5059529718 @default.
- W2562585861 creator A5062353476 @default.
- W2562585861 creator A5080710161 @default.
- W2562585861 creator A5091016923 @default.
- W2562585861 creator A5091908601 @default.
- W2562585861 date "2016-12-21" @default.
- W2562585861 modified "2023-09-24" @default.
- W2562585861 title "The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors" @default.
- W2562585861 cites W1833855516 @default.
- W2562585861 cites W1902775329 @default.
- W2562585861 cites W1971513938 @default.
- W2562585861 cites W1980983414 @default.
- W2562585861 cites W1991766235 @default.
- W2562585861 cites W2009925245 @default.
- W2562585861 cites W2014779151 @default.
- W2562585861 cites W2020184426 @default.
- W2562585861 cites W2021842829 @default.
- W2562585861 cites W2068692900 @default.
- W2562585861 cites W2084567915 @default.
- W2562585861 cites W2090552744 @default.
- W2562585861 cites W2098742258 @default.
- W2562585861 cites W2099220357 @default.
- W2562585861 cites W2099863319 @default.
- W2562585861 cites W2109158162 @default.
- W2562585861 cites W2110107835 @default.
- W2562585861 cites W2120380781 @default.
- W2562585861 cites W2138697369 @default.
- W2562585861 cites W2187601352 @default.
- W2562585861 cites W2201997235 @default.
- W2562585861 cites W2312227080 @default.
- W2562585861 cites W2332782557 @default.
- W2562585861 cites W2344465921 @default.
- W2562585861 cites W2405617887 @default.
- W2562585861 cites W2416532421 @default.
- W2562585861 cites W2469169305 @default.
- W2562585861 cites W2564407574 @default.
- W2562585861 cites W3025891904 @default.
- W2562585861 cites W4327493786 @default.
- W2562585861 doi "https://doi.org/10.1021/acs.jmedchem.6b01496" @default.
- W2562585861 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28001399" @default.
- W2562585861 hasPublicationYear "2016" @default.
- W2562585861 type Work @default.
- W2562585861 sameAs 2562585861 @default.
- W2562585861 citedByCount "29" @default.
- W2562585861 countsByYear W25625858612017 @default.
- W2562585861 countsByYear W25625858612018 @default.
- W2562585861 countsByYear W25625858612019 @default.
- W2562585861 countsByYear W25625858612020 @default.
- W2562585861 countsByYear W25625858612021 @default.
- W2562585861 countsByYear W25625858612022 @default.
- W2562585861 countsByYear W25625858612023 @default.
- W2562585861 crossrefType "journal-article" @default.
- W2562585861 hasAuthorship W2562585861A5006698956 @default.
- W2562585861 hasAuthorship W2562585861A5007100513 @default.
- W2562585861 hasAuthorship W2562585861A5008080434 @default.
- W2562585861 hasAuthorship W2562585861A5009300129 @default.
- W2562585861 hasAuthorship W2562585861A5009651273 @default.
- W2562585861 hasAuthorship W2562585861A5011428138 @default.
- W2562585861 hasAuthorship W2562585861A5022466041 @default.
- W2562585861 hasAuthorship W2562585861A5022499603 @default.
- W2562585861 hasAuthorship W2562585861A5027760014 @default.
- W2562585861 hasAuthorship W2562585861A5028265641 @default.
- W2562585861 hasAuthorship W2562585861A5032337429 @default.
- W2562585861 hasAuthorship W2562585861A5032342352 @default.
- W2562585861 hasAuthorship W2562585861A5034056485 @default.
- W2562585861 hasAuthorship W2562585861A5037496059 @default.
- W2562585861 hasAuthorship W2562585861A5044962386 @default.
- W2562585861 hasAuthorship W2562585861A5049963165 @default.
- W2562585861 hasAuthorship W2562585861A5051379817 @default.
- W2562585861 hasAuthorship W2562585861A5059529718 @default.
- W2562585861 hasAuthorship W2562585861A5062353476 @default.
- W2562585861 hasAuthorship W2562585861A5080710161 @default.
- W2562585861 hasAuthorship W2562585861A5091016923 @default.
- W2562585861 hasAuthorship W2562585861A5091908601 @default.
- W2562585861 hasConcept C164718446 @default.
- W2562585861 hasConcept C166342909 @default.
- W2562585861 hasConcept C170493617 @default.
- W2562585861 hasConcept C185592680 @default.
- W2562585861 hasConcept C2777756961 @default.