FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2987348921> ?p ?o ?g. }

• W2987348921 endingPage "e0007693" @default.
• W2987348921 startingPage "e0007693" @default.
• W2987348921 abstract "Background Praziquantel represents the frontline chemotherapy used to treat schistosomiasis, a neglected tropical disease (NTD) caused by infection with macro-parasitic blood fluke schistosomes. While this drug is safe, its inability to kill all schistosome lifecycle stages within the human host often requires repeat treatments. This limitation, amongst others, has led to the search for novel anti-schistosome replacement or combinatorial chemotherapies. Here, we describe a repositioning strategy to assess the anthelmintic activity of epigenetic probes/inhibitors obtained from the Structural Genomics Consortium. Methodology/Principle findings Thirty-seven epigenetic probes/inhibitors targeting histone readers, writers and erasers were initially screened against Schistosoma mansoni schistosomula using the high-throughput Roboworm platform. At 10 μM, 14 of these 37 compounds (38%) negatively affected schistosomula motility and phenotype after 72 hours of continuous co-incubation. Subsequent dose-response titrations against schistosomula and adult worms revealed epigenetic probes targeting one reader (NVS-CECR2-1), one writer (LLY-507 and BAY-598) and one eraser (GSK-J4) to be particularly active. As LLY-507/BAY-598 (SMYD2 histone methyltransferase inhibitors) and GSK-J4 (a JMJD3 histone demethylase inhibitor) regulate an epigenetic process (protein methylation) known to be critical for schistosome development, further characterisation of these compounds/putative targets was performed. RNA interference (RNAi) of one putative LLY-507/BAY-598 S. mansoni target (Smp_000700) in adult worms replicated the compound-mediated motility and egg production defects. Furthermore, H3K36me2, a known product catalysed by SMYD2 activity, was also reduced by LLY-507 (25%), BAY-598 (23%) and siSmp_000700 (15%) treatment of adult worms. Oviposition and packaging of vitelline cells into in vitro laid eggs was also significantly affected by GSK-J4 (putative cell permeable prodrug inhibitor of Smp_034000), but not by the related structural analogue GSK-J1 (cell impermeable inhibitor). Conclusion/Significance Collectively, these results provide further support for the development of next-generation drugs targeting schistosome epigenetic pathway components. In particular, the progression of histone methylation/demethylation modulators presents a tractable strategy for anti-schistosomal control." @default.
• W2987348921 created "2019-11-22" @default.
• W2987348921 creator A5015558146 @default.
• W2987348921 creator A5017758211 @default.
• W2987348921 creator A5019969243 @default.
• W2987348921 creator A5023996497 @default.
• W2987348921 creator A5024572338 @default.
• W2987348921 creator A5045424288 @default.
• W2987348921 creator A5057959292 @default.
• W2987348921 creator A5065365203 @default.
• W2987348921 creator A5073879658 @default.
• W2987348921 creator A5084976731 @default.
• W2987348921 date "2019-11-15" @default.
• W2987348921 modified "2023-09-27" @default.
• W2987348921 title "The repositioning of epigenetic probes/inhibitors identifies new anti-schistosomal lead compounds and chemotherapeutic targets" @default.
• W2987348921 cites W1549521886 @default.
• W2987348921 cites W1825132503 @default.
• W2987348921 cites W1835221221 @default.
• W2987348921 cites W1945410182 @default.
• W2987348921 cites W1964248507 @default.
• W2987348921 cites W1968217711 @default.
• W2987348921 cites W1970632869 @default.
• W2987348921 cites W1976717554 @default.
• W2987348921 cites W1977199336 @default.
• W2987348921 cites W1978867804 @default.
• W2987348921 cites W1982682419 @default.
• W2987348921 cites W1988870225 @default.
• W2987348921 cites W1990149359 @default.
• W2987348921 cites W1991474023 @default.
• W2987348921 cites W1992192767 @default.
• W2987348921 cites W1997403578 @default.
• W2987348921 cites W2006252452 @default.
• W2987348921 cites W2037201757 @default.
• W2987348921 cites W2041535798 @default.
• W2987348921 cites W2054301876 @default.
• W2987348921 cites W2055423985 @default.
• W2987348921 cites W2056562833 @default.
• W2987348921 cites W2062927905 @default.
• W2987348921 cites W2063756876 @default.
• W2987348921 cites W2073666805 @default.
• W2987348921 cites W2074986801 @default.
• W2987348921 cites W2085460412 @default.
• W2987348921 cites W2098664990 @default.
• W2987348921 cites W2102993309 @default.
• W2987348921 cites W2105406802 @default.
• W2987348921 cites W2106882534 @default.
• W2987348921 cites W2118746801 @default.
• W2987348921 cites W2120772351 @default.
• W2987348921 cites W2124470043 @default.
• W2987348921 cites W2127989042 @default.
• W2987348921 cites W2132926880 @default.
• W2987348921 cites W2137429553 @default.
• W2987348921 cites W2140895961 @default.
• W2987348921 cites W2144193004 @default.
• W2987348921 cites W2144400965 @default.
• W2987348921 cites W2154744452 @default.
• W2987348921 cites W2160697532 @default.
• W2987348921 cites W2166164324 @default.
• W2987348921 cites W2169568557 @default.
• W2987348921 cites W2179282661 @default.
• W2987348921 cites W2286718346 @default.
• W2987348921 cites W2289047474 @default.
• W2987348921 cites W2311203695 @default.
• W2987348921 cites W2326166619 @default.
• W2987348921 cites W2337020460 @default.
• W2987348921 cites W2394955156 @default.
• W2987348921 cites W2531288146 @default.
• W2987348921 cites W2548964193 @default.
• W2987348921 cites W2563930191 @default.
• W2987348921 cites W2579472951 @default.
• W2987348921 cites W2607485550 @default.
• W2987348921 cites W2614163602 @default.
• W2987348921 cites W2621379905 @default.
• W2987348921 cites W2745897864 @default.
• W2987348921 cites W2753025542 @default.
• W2987348921 cites W2770931274 @default.
• W2987348921 cites W2793900979 @default.
• W2987348921 cites W2794584771 @default.
• W2987348921 cites W2802302687 @default.
• W2987348921 cites W2804621369 @default.
• W2987348921 cites W2809810794 @default.
• W2987348921 cites W2898256948 @default.
• W2987348921 cites W2898324010 @default.
• W2987348921 cites W2900793673 @default.
• W2987348921 cites W2953288458 @default.
• W2987348921 cites W4211000692 @default.
• W2987348921 cites W4211093028 @default.
• W2987348921 cites W4211128418 @default.
• W2987348921 cites W4230779439 @default.
• W2987348921 cites W4246356731 @default.
• W2987348921 doi "https://doi.org/10.1371/journal.pntd.0007693" @default.
• W2987348921 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6881072" @default.
• W2987348921 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31730617" @default.
• W2987348921 hasPublicationYear "2019" @default.
• W2987348921 type Work @default.
• W2987348921 sameAs 2987348921 @default.
• W2987348921 citedByCount "22" @default.
• W2987348921 countsByYear W29873489212020 @default.

• next