Matches in SemOpenAlex for { <https://semopenalex.org/work/W2048265770> ?p ?o ?g. }
- W2048265770 endingPage "8048" @default.
- W2048265770 startingPage "8032" @default.
- W2048265770 abstract "Inhibition of mixed lineage kinase 3 (MLK3) is a potential strategy for treatment of Parkinson’s disease and HIV-1 associated neurocognitive disorders (HAND), requiring an inhibitor that can achieve significant brain concentration levels. We report here URMC-099 (1) an orally bioavailable (F = 41%), potent (IC50 = 14 nM) MLK3 inhibitor with excellent brain exposure in mouse PK models and minimal interference with key human CYP450 enzymes or hERG channels. The compound inhibits LPS-induced TNFα release in microglial cells, HIV-1 Tat-induced release of cytokines in human monocytes and up-regulation of phospho-JNK in Tat-injected brains of mice. Compound 1 likely functions in HAND preclinical models by inhibiting multiple kinase pathways, including MLK3 and LRRK2 (IC50 = 11 nM). We compare the kinase specificity and BBB penetration of 1 with CEP-1347 (2). Compound 1 is well tolerated, with excellent in vivo activity in HAND models, and is under investigation for further development." @default.
- W2048265770 created "2016-06-24" @default.
- W2048265770 creator A5009468541 @default.
- W2048265770 creator A5028926950 @default.
- W2048265770 creator A5031088799 @default.
- W2048265770 creator A5033967453 @default.
- W2048265770 creator A5042739196 @default.
- W2048265770 creator A5049187488 @default.
- W2048265770 creator A5073227816 @default.
- W2048265770 creator A5074202938 @default.
- W2048265770 creator A5074490683 @default.
- W2048265770 creator A5074868381 @default.
- W2048265770 creator A5076980543 @default.
- W2048265770 creator A5087695899 @default.
- W2048265770 creator A5090081574 @default.
- W2048265770 date "2013-10-03" @default.
- W2048265770 modified "2023-09-29" @default.
- W2048265770 title "Discovery, Synthesis, and Characterization of an Orally Bioavailable, Brain Penetrant Inhibitor of Mixed Lineage Kinase 3" @default.
- W2048265770 cites W1489137899 @default.
- W2048265770 cites W1495575342 @default.
- W2048265770 cites W1530364137 @default.
- W2048265770 cites W1539290896 @default.
- W2048265770 cites W1596539802 @default.
- W2048265770 cites W1833727709 @default.
- W2048265770 cites W1909901392 @default.
- W2048265770 cites W1964892539 @default.
- W2048265770 cites W1965394539 @default.
- W2048265770 cites W1965811513 @default.
- W2048265770 cites W1972452204 @default.
- W2048265770 cites W1973711355 @default.
- W2048265770 cites W1973763912 @default.
- W2048265770 cites W1982600877 @default.
- W2048265770 cites W1987871624 @default.
- W2048265770 cites W1988487618 @default.
- W2048265770 cites W2006002450 @default.
- W2048265770 cites W2011884125 @default.
- W2048265770 cites W2012828222 @default.
- W2048265770 cites W2014582878 @default.
- W2048265770 cites W2016036211 @default.
- W2048265770 cites W2016613470 @default.
- W2048265770 cites W2022185380 @default.
- W2048265770 cites W2026924553 @default.
- W2048265770 cites W2035322574 @default.
- W2048265770 cites W2035394056 @default.
- W2048265770 cites W2042962510 @default.
- W2048265770 cites W2048531806 @default.
- W2048265770 cites W2050660106 @default.
- W2048265770 cites W2051305184 @default.
- W2048265770 cites W2055437587 @default.
- W2048265770 cites W2056148985 @default.
- W2048265770 cites W2063511018 @default.
- W2048265770 cites W2067643341 @default.
- W2048265770 cites W2072392477 @default.
- W2048265770 cites W2076174549 @default.
- W2048265770 cites W2077012020 @default.
- W2048265770 cites W2085054050 @default.
- W2048265770 cites W2086286404 @default.
- W2048265770 cites W2091654078 @default.
- W2048265770 cites W2092018624 @default.
- W2048265770 cites W2095726706 @default.
- W2048265770 cites W2097972613 @default.
- W2048265770 cites W2100772783 @default.
- W2048265770 cites W2117667168 @default.
- W2048265770 cites W2119628249 @default.
- W2048265770 cites W2126893023 @default.
- W2048265770 cites W2130117483 @default.
- W2048265770 cites W2130599091 @default.
- W2048265770 cites W2132970977 @default.
- W2048265770 cites W2133655326 @default.
- W2048265770 cites W2138012613 @default.
- W2048265770 cites W2146133466 @default.
- W2048265770 cites W2153142245 @default.
- W2048265770 cites W2154173754 @default.
- W2048265770 cites W2161017525 @default.
- W2048265770 cites W2163094044 @default.
- W2048265770 cites W2790805946 @default.
- W2048265770 cites W4233451333 @default.
- W2048265770 doi "https://doi.org/10.1021/jm401094t" @default.
- W2048265770 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4032177" @default.
- W2048265770 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24044867" @default.
- W2048265770 hasPublicationYear "2013" @default.
- W2048265770 type Work @default.
- W2048265770 sameAs 2048265770 @default.
- W2048265770 citedByCount "65" @default.
- W2048265770 countsByYear W20482657702013 @default.
- W2048265770 countsByYear W20482657702014 @default.
- W2048265770 countsByYear W20482657702015 @default.
- W2048265770 countsByYear W20482657702016 @default.
- W2048265770 countsByYear W20482657702017 @default.
- W2048265770 countsByYear W20482657702018 @default.
- W2048265770 countsByYear W20482657702019 @default.
- W2048265770 countsByYear W20482657702020 @default.
- W2048265770 countsByYear W20482657702021 @default.
- W2048265770 countsByYear W20482657702022 @default.
- W2048265770 countsByYear W20482657702023 @default.
- W2048265770 crossrefType "journal-article" @default.
- W2048265770 hasAuthorship W2048265770A5009468541 @default.
- W2048265770 hasAuthorship W2048265770A5028926950 @default.