Matches in SemOpenAlex for { <https://semopenalex.org/work/W2772202291> ?p ?o ?g. }
- W2772202291 endingPage "629" @default.
- W2772202291 startingPage "615" @default.
- W2772202291 abstract "Pyridoquinazolinecarboxamides have been reported as RNA polymerase I inhibitors and represent a novel class of potential antitumor agents. BMH-21, was reported to intercalate with GC-rich rDNA, resulting in nucleolar stress as a primary mechanism of cytotoxicity. The interaction of BMH-21 and analogues with DNA G-quadruplex structures was studied by NMR and molecular modelling. The cellular response was investigated in a panel of human tumor cell lines and protein expression was examined by Western Blot analysis. We explored the ability of BMH-21 and its analogue 2 to bind to G-quadruplex present in the c-MYC promoter, by NMR and molecular modelling studies. We provide evidence that both compounds are not typical DNA intercalators but are effective binders of the tested G-quadruplex. The interaction with c-MYC G-quadruplex was reflected in down-regulation of c-Myc expression in human tumor cells. The inhibitory effect was almost complete in lymphoma cells SUDHL4 characterized by overexpression of c-Myc protein. This downregulation reflected an early and persistent modulation of cMyc mRNA. Given the relevance of c-MYC in regulation of ribosome biogenesis, it is conceivable that the inhibition of c-MYC contributes to the perturbation of nuclear functions and RNA polymerase I activity. Similar experiments with CX-5461, another RNA polymerase I transcription inhibitor, indicate the same behaviour in G-quadruplex stabilization. Our results support the hypothesis that BMH-21 and analogue compounds share the same mechanism, i.e. G-quadruplex binding as a primary event of a cascade leading to inhibition of RNA polymerase I and apoptosis." @default.
- W2772202291 created "2017-12-22" @default.
- W2772202291 creator A5023876020 @default.
- W2772202291 creator A5025424906 @default.
- W2772202291 creator A5033312783 @default.
- W2772202291 creator A5036601947 @default.
- W2772202291 creator A5053389850 @default.
- W2772202291 creator A5063842317 @default.
- W2772202291 creator A5066576514 @default.
- W2772202291 creator A5067068751 @default.
- W2772202291 creator A5071576099 @default.
- W2772202291 date "2018-03-01" @default.
- W2772202291 modified "2023-10-14" @default.
- W2772202291 title "c-MYC G-quadruplex binding by the RNA polymerase I inhibitor BMH-21 and analogues revealed by a combined NMR and biochemical Approach" @default.
- W2772202291 cites W1531154876 @default.
- W2772202291 cites W1966834115 @default.
- W2772202291 cites W1966841369 @default.
- W2772202291 cites W1977617601 @default.
- W2772202291 cites W1980373840 @default.
- W2772202291 cites W1983506450 @default.
- W2772202291 cites W1985698480 @default.
- W2772202291 cites W1990635146 @default.
- W2772202291 cites W2003477078 @default.
- W2772202291 cites W2008517160 @default.
- W2772202291 cites W2014645134 @default.
- W2772202291 cites W2020374412 @default.
- W2772202291 cites W2025248257 @default.
- W2772202291 cites W2029140710 @default.
- W2772202291 cites W2033742799 @default.
- W2772202291 cites W2035667154 @default.
- W2772202291 cites W2043720815 @default.
- W2772202291 cites W2048368558 @default.
- W2772202291 cites W2050913592 @default.
- W2772202291 cites W2056072994 @default.
- W2772202291 cites W2063270472 @default.
- W2772202291 cites W2063733156 @default.
- W2772202291 cites W2069543945 @default.
- W2772202291 cites W2074139680 @default.
- W2772202291 cites W2074615820 @default.
- W2772202291 cites W2092511209 @default.
- W2772202291 cites W2097521277 @default.
- W2772202291 cites W2100013366 @default.
- W2772202291 cites W2100734715 @default.
- W2772202291 cites W2100893053 @default.
- W2772202291 cites W2120344444 @default.
- W2772202291 cites W2123768693 @default.
- W2772202291 cites W2123859926 @default.
- W2772202291 cites W2129104457 @default.
- W2772202291 cites W2149839082 @default.
- W2772202291 cites W2151510603 @default.
- W2772202291 cites W2155366353 @default.
- W2772202291 cites W2156506178 @default.
- W2772202291 cites W2163134391 @default.
- W2772202291 cites W2165526004 @default.
- W2772202291 cites W2281334232 @default.
- W2772202291 cites W2335766382 @default.
- W2772202291 cites W2601051489 @default.
- W2772202291 cites W2605336071 @default.
- W2772202291 cites W2951392003 @default.
- W2772202291 doi "https://doi.org/10.1016/j.bbagen.2017.12.002" @default.
- W2772202291 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29229300" @default.
- W2772202291 hasPublicationYear "2018" @default.
- W2772202291 type Work @default.
- W2772202291 sameAs 2772202291 @default.
- W2772202291 citedByCount "27" @default.
- W2772202291 countsByYear W27722022912018 @default.
- W2772202291 countsByYear W27722022912019 @default.
- W2772202291 countsByYear W27722022912020 @default.
- W2772202291 countsByYear W27722022912021 @default.
- W2772202291 countsByYear W27722022912022 @default.
- W2772202291 countsByYear W27722022912023 @default.
- W2772202291 crossrefType "journal-article" @default.
- W2772202291 hasAuthorship W2772202291A5023876020 @default.
- W2772202291 hasAuthorship W2772202291A5025424906 @default.
- W2772202291 hasAuthorship W2772202291A5033312783 @default.
- W2772202291 hasAuthorship W2772202291A5036601947 @default.
- W2772202291 hasAuthorship W2772202291A5053389850 @default.
- W2772202291 hasAuthorship W2772202291A5063842317 @default.
- W2772202291 hasAuthorship W2772202291A5066576514 @default.
- W2772202291 hasAuthorship W2772202291A5067068751 @default.
- W2772202291 hasAuthorship W2772202291A5071576099 @default.
- W2772202291 hasConcept C101762097 @default.
- W2772202291 hasConcept C104317684 @default.
- W2772202291 hasConcept C138885662 @default.
- W2772202291 hasConcept C150194340 @default.
- W2772202291 hasConcept C153911025 @default.
- W2772202291 hasConcept C179926584 @default.
- W2772202291 hasConcept C185592680 @default.
- W2772202291 hasConcept C25281209 @default.
- W2772202291 hasConcept C2776415932 @default.
- W2772202291 hasConcept C41258723 @default.
- W2772202291 hasConcept C41895202 @default.
- W2772202291 hasConcept C552990157 @default.
- W2772202291 hasConcept C55493867 @default.
- W2772202291 hasConcept C64350747 @default.
- W2772202291 hasConcept C67705224 @default.
- W2772202291 hasConcept C82381507 @default.
- W2772202291 hasConcept C86803240 @default.