Matches in SemOpenAlex for { <https://semopenalex.org/work/W2557257112> ?p ?o ?g. }
- W2557257112 endingPage "113" @default.
- W2557257112 startingPage "102" @default.
- W2557257112 abstract "The canonical NF-κB signaling pathway is a mediator of the cellular inflammatory response and a target for developing therapeutics for multiple human diseases. The furthest downstream proteins in the pathway, the p50/p65 transcription factor heterodimer, have been recalcitrant toward small molecule inhibition despite the substantial number of compounds known to inhibit upstream proteins in the activation pathway. Given the roles of many of these upstream proteins in multiple biochemical pathways, targeting the p50/p65 heterodimer offers an opportunity for enhanced on-target specificity. Toward this end, the p65 protein presents two nondisulfide cysteines, Cys38 and Cys120, at its DNA-binding interface that are amenable to targeting by covalent molecules. The natural product helenalin, a sesquiterpene lactone, has been previously shown to target Cys38 on p65 and ablate its DNA-binding ability. Using helenalin as inspiration, simplified helenalin analogues were designed, synthesized, and shown to inhibit induced canonical NF-κB signaling in cell culture. Moreover, two simplified helenalin probes were proficient at forming covalent protein adducts, binding to Cys38 on recombinant p65, and targeting p65 in HeLa cells without engaging canonical NF-κB signaling proteins IκBα, p50, and IKKα/β. These studies further support that targeting the p65 transcription factor-DNA interface with covalent small molecule inhibitors is a viable approach toward regulating canonical NF-κB signaling." @default.
- W2557257112 created "2016-12-08" @default.
- W2557257112 creator A5009655060 @default.
- W2557257112 creator A5015278922 @default.
- W2557257112 creator A5016244640 @default.
- W2557257112 creator A5060437000 @default.
- W2557257112 date "2016-11-28" @default.
- W2557257112 modified "2023-09-28" @default.
- W2557257112 title "Targeting NF-κB p65 with a Helenalin Inspired Bis-electrophile" @default.
- W2557257112 cites W1504155896 @default.
- W2557257112 cites W1964862845 @default.
- W2557257112 cites W1968791351 @default.
- W2557257112 cites W1969736018 @default.
- W2557257112 cites W1971225062 @default.
- W2557257112 cites W1972425323 @default.
- W2557257112 cites W1973354681 @default.
- W2557257112 cites W1991297121 @default.
- W2557257112 cites W1991366673 @default.
- W2557257112 cites W1996193183 @default.
- W2557257112 cites W1998859103 @default.
- W2557257112 cites W2000252737 @default.
- W2557257112 cites W2002866108 @default.
- W2557257112 cites W2003818487 @default.
- W2557257112 cites W2007539521 @default.
- W2557257112 cites W2018514966 @default.
- W2557257112 cites W2024964682 @default.
- W2557257112 cites W2027704988 @default.
- W2557257112 cites W2037337913 @default.
- W2557257112 cites W2040101825 @default.
- W2557257112 cites W2042943489 @default.
- W2557257112 cites W2043765788 @default.
- W2557257112 cites W2043892945 @default.
- W2557257112 cites W2048785097 @default.
- W2557257112 cites W2051014544 @default.
- W2557257112 cites W2052857028 @default.
- W2557257112 cites W2060987284 @default.
- W2557257112 cites W2068854551 @default.
- W2557257112 cites W2069194725 @default.
- W2557257112 cites W2069562068 @default.
- W2557257112 cites W2073679908 @default.
- W2557257112 cites W2077399025 @default.
- W2557257112 cites W2078594804 @default.
- W2557257112 cites W2083594362 @default.
- W2557257112 cites W2083932946 @default.
- W2557257112 cites W2084183850 @default.
- W2557257112 cites W2085016194 @default.
- W2557257112 cites W20888715 @default.
- W2557257112 cites W2090889931 @default.
- W2557257112 cites W2093486996 @default.
- W2557257112 cites W2094863064 @default.
- W2557257112 cites W2098962649 @default.
- W2557257112 cites W2110440735 @default.
- W2557257112 cites W2119109189 @default.
- W2557257112 cites W2119723870 @default.
- W2557257112 cites W2120649027 @default.
- W2557257112 cites W2125678075 @default.
- W2557257112 cites W2143945519 @default.
- W2557257112 cites W2145662716 @default.
- W2557257112 cites W2145942270 @default.
- W2557257112 cites W2146373235 @default.
- W2557257112 cites W2155290347 @default.
- W2557257112 cites W2156279513 @default.
- W2557257112 cites W2157032737 @default.
- W2557257112 cites W2273297521 @default.
- W2557257112 cites W2317233719 @default.
- W2557257112 cites W2319379232 @default.
- W2557257112 cites W2336869895 @default.
- W2557257112 cites W2343511794 @default.
- W2557257112 cites W2389545375 @default.
- W2557257112 cites W2415257729 @default.
- W2557257112 cites W2526268427 @default.
- W2557257112 cites W2949112880 @default.
- W2557257112 cites W2950853462 @default.
- W2557257112 cites W2953280598 @default.
- W2557257112 cites W3005284946 @default.
- W2557257112 cites W3005484856 @default.
- W2557257112 cites W4253973392 @default.
- W2557257112 cites W560094640 @default.
- W2557257112 doi "https://doi.org/10.1021/acschembio.6b00751" @default.
- W2557257112 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5357558" @default.
- W2557257112 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28103680" @default.
- W2557257112 hasPublicationYear "2016" @default.
- W2557257112 type Work @default.
- W2557257112 sameAs 2557257112 @default.
- W2557257112 citedByCount "28" @default.
- W2557257112 countsByYear W25572571122017 @default.
- W2557257112 countsByYear W25572571122018 @default.
- W2557257112 countsByYear W25572571122019 @default.
- W2557257112 countsByYear W25572571122020 @default.
- W2557257112 countsByYear W25572571122021 @default.
- W2557257112 countsByYear W25572571122022 @default.
- W2557257112 countsByYear W25572571122023 @default.
- W2557257112 crossrefType "journal-article" @default.
- W2557257112 hasAuthorship W2557257112A5009655060 @default.
- W2557257112 hasAuthorship W2557257112A5015278922 @default.
- W2557257112 hasAuthorship W2557257112A5016244640 @default.
- W2557257112 hasAuthorship W2557257112A5060437000 @default.
- W2557257112 hasBestOaLocation W25572571122 @default.