Matches in SemOpenAlex for { <https://semopenalex.org/work/W2116918062> ?p ?o ?g. }
- W2116918062 endingPage "7486" @default.
- W2116918062 startingPage "7475" @default.
- W2116918062 abstract "Histone deacetylases (HDAC) that regulate gene expression are being explored as cancer therapeutic targets. In this study, we focused on HDAC6 based on its ability to inhibit cancerous Hsp90 chaperone activities by disrupting Hsp90/p23 interactions. To identify novel HDAC6 inhibitors, we used a dual-luciferase reporter system in cell culture and living mice by bioluminescence imaging (BLI). On the basis of existing knowledge, a library of hydrazone compounds was generated for screening by coupling cinnamic hydroxamates with aldehydes and ketones. Potency and selectivity were determined by in vitro HDAC profiling assays, with further evaluation to inhibit Hsp90(α/β)/p23 interactions by BLI. In this manner, we identified compound 1A12 as a dose-dependent inhibitor of Hsp90(α/β)/p23 interactions, UKE-1 myeloid cell proliferation, p21(waf1) upregulation, and acetylated histone H3 levels. 1A12 was efficacious in tumor xenografts expressing Hsp90(α)/p23 reporters relative to carrier control-treated mice as determined by BLI. Small animal (18)F-FDG PET/CT imaging on the same cohort showed that 1A12 also inhibited glucose metabolism relative to control subjects. Ex vivo analyses of tumor lysates showed that 1A12 administration upregulated acetylated-H3 by approximately 3.5-fold. Taken together, our results describe the discovery and initial preclinical validation of a novel selective HDAC inhibitor." @default.
- W2116918062 created "2016-06-24" @default.
- W2116918062 creator A5018071576 @default.
- W2116918062 creator A5018880989 @default.
- W2116918062 creator A5019955301 @default.
- W2116918062 creator A5035618234 @default.
- W2116918062 creator A5037115007 @default.
- W2116918062 creator A5040925962 @default.
- W2116918062 creator A5046780897 @default.
- W2116918062 creator A5048102295 @default.
- W2116918062 creator A5053711959 @default.
- W2116918062 creator A5067096193 @default.
- W2116918062 creator A5072926885 @default.
- W2116918062 creator A5083002573 @default.
- W2116918062 date "2014-10-15" @default.
- W2116918062 modified "2023-10-12" @default.
- W2116918062 title "Syntheses and Discovery of a Novel Class of Cinnamic Hydroxamates as Histone Deacetylase Inhibitors by Multimodality Molecular Imaging in Living Subjects" @default.
- W2116918062 cites W1861243942 @default.
- W2116918062 cites W1973962086 @default.
- W2116918062 cites W1974575376 @default.
- W2116918062 cites W1978205433 @default.
- W2116918062 cites W1982580601 @default.
- W2116918062 cites W1988606508 @default.
- W2116918062 cites W1990011854 @default.
- W2116918062 cites W1990707496 @default.
- W2116918062 cites W1991660464 @default.
- W2116918062 cites W1992599219 @default.
- W2116918062 cites W199669094 @default.
- W2116918062 cites W2004478552 @default.
- W2116918062 cites W2013588595 @default.
- W2116918062 cites W2022303284 @default.
- W2116918062 cites W2053638053 @default.
- W2116918062 cites W2056181814 @default.
- W2116918062 cites W2059526410 @default.
- W2116918062 cites W2063065954 @default.
- W2116918062 cites W2068257081 @default.
- W2116918062 cites W2068408712 @default.
- W2116918062 cites W2069123340 @default.
- W2116918062 cites W2069683864 @default.
- W2116918062 cites W2071380029 @default.
- W2116918062 cites W2071559249 @default.
- W2116918062 cites W2081106175 @default.
- W2116918062 cites W2081484203 @default.
- W2116918062 cites W2083784041 @default.
- W2116918062 cites W2087961967 @default.
- W2116918062 cites W2090168046 @default.
- W2116918062 cites W2091885586 @default.
- W2116918062 cites W2098956821 @default.
- W2116918062 cites W2099875690 @default.
- W2116918062 cites W2101127235 @default.
- W2116918062 cites W2102650381 @default.
- W2116918062 cites W2105906697 @default.
- W2116918062 cites W2109329999 @default.
- W2116918062 cites W2111013340 @default.
- W2116918062 cites W2124813986 @default.
- W2116918062 cites W2148063684 @default.
- W2116918062 cites W2152831388 @default.
- W2116918062 cites W2158178080 @default.
- W2116918062 cites W2159317665 @default.
- W2116918062 cites W2160451428 @default.
- W2116918062 cites W2164453551 @default.
- W2116918062 cites W2166628771 @default.
- W2116918062 cites W2168968323 @default.
- W2116918062 cites W2169765840 @default.
- W2116918062 cites W2312775223 @default.
- W2116918062 cites W2318317030 @default.
- W2116918062 cites W2038477243 @default.
- W2116918062 doi "https://doi.org/10.1158/0008-5472.can-14-0197" @default.
- W2116918062 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4315624" @default.
- W2116918062 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25320008" @default.
- W2116918062 hasPublicationYear "2014" @default.
- W2116918062 type Work @default.
- W2116918062 sameAs 2116918062 @default.
- W2116918062 citedByCount "11" @default.
- W2116918062 countsByYear W21169180622015 @default.
- W2116918062 countsByYear W21169180622016 @default.
- W2116918062 countsByYear W21169180622017 @default.
- W2116918062 countsByYear W21169180622018 @default.
- W2116918062 countsByYear W21169180622020 @default.
- W2116918062 countsByYear W21169180622021 @default.
- W2116918062 crossrefType "journal-article" @default.
- W2116918062 hasAuthorship W2116918062A5018071576 @default.
- W2116918062 hasAuthorship W2116918062A5018880989 @default.
- W2116918062 hasAuthorship W2116918062A5019955301 @default.
- W2116918062 hasAuthorship W2116918062A5035618234 @default.
- W2116918062 hasAuthorship W2116918062A5037115007 @default.
- W2116918062 hasAuthorship W2116918062A5040925962 @default.
- W2116918062 hasAuthorship W2116918062A5046780897 @default.
- W2116918062 hasAuthorship W2116918062A5048102295 @default.
- W2116918062 hasAuthorship W2116918062A5053711959 @default.
- W2116918062 hasAuthorship W2116918062A5067096193 @default.
- W2116918062 hasAuthorship W2116918062A5072926885 @default.
- W2116918062 hasAuthorship W2116918062A5083002573 @default.
- W2116918062 hasBestOaLocation W21169180621 @default.
- W2116918062 hasConcept C104317684 @default.
- W2116918062 hasConcept C111335760 @default.
- W2116918062 hasConcept C119157956 @default.
- W2116918062 hasConcept C127561419 @default.