FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2318477319> ?p ?o ?g. }

• W2318477319 endingPage "1876" @default.
• W2318477319 startingPage "1869" @default.
• W2318477319 abstract "The ubiquitin-proteasome system (UPS) is a potential pathway for therapeutic intervention for pathogens such as Plasmodium, the causative agent of malaria. However, due to the essential nature of this proteolytic pathway, proteasome inhibitors must avoid inhibition of the host enzyme complex to prevent toxic side effects. The Plasmodium proteasome is poorly characterized, making rational design of inhibitors that induce selective parasite killing difficult. In this study, we developed a chemical probe that labels all catalytic sites of the Plasmodium proteasome. Using this probe, we identified several subunit selective small molecule inhibitors of the parasite enzyme complex. Treatment with an inhibitor that is specific for the β5 subunit during blood stage schizogony led to a dramatic decrease in parasite replication while short-term inhibition of the β2 subunit did not affect viability. Interestingly, coinhibition of both the β2 and β5 catalytic subunits resulted in enhanced parasite killing at all stages of the blood stage life cycle and reduced parasite levels in vivo to barely detectable levels. Parasite killing was achieved with overall low host toxicity, something that has not been possible with existing proteasome inhibitors. Our results highlight differences in the subunit dependency of the parasite and human proteasome, thus providing a strategy for development of potent antimalarial drugs with overall low host toxicity." @default.
• W2318477319 created "2016-06-24" @default.
• W2318477319 creator A5000584872 @default.
• W2318477319 creator A5003559845 @default.
• W2318477319 creator A5005370974 @default.
• W2318477319 creator A5005853846 @default.
• W2318477319 creator A5009402514 @default.
• W2318477319 creator A5019560977 @default.
• W2318477319 creator A5031836660 @default.
• W2318477319 creator A5056673744 @default.
• W2318477319 creator A5069804033 @default.
• W2318477319 creator A5080458286 @default.
• W2318477319 date "2014-06-19" @default.
• W2318477319 modified "2023-10-11" @default.
• W2318477319 title "Assessing Subunit Dependency of the <i>Plasmodium</i> Proteasome Using Small Molecule Inhibitors and Active Site Probes" @default.
• W2318477319 cites W1964499210 @default.
• W2318477319 cites W1965575777 @default.
• W2318477319 cites W1965790877 @default.
• W2318477319 cites W1969894269 @default.
• W2318477319 cites W1975731136 @default.
• W2318477319 cites W1983275249 @default.
• W2318477319 cites W1986036865 @default.
• W2318477319 cites W1991558827 @default.
• W2318477319 cites W1993201799 @default.
• W2318477319 cites W1996091402 @default.
• W2318477319 cites W1998526841 @default.
• W2318477319 cites W1999042605 @default.
• W2318477319 cites W2009504763 @default.
• W2318477319 cites W2010440422 @default.
• W2318477319 cites W2019116906 @default.
• W2318477319 cites W2032634258 @default.
• W2318477319 cites W2042801252 @default.
• W2318477319 cites W2047650149 @default.
• W2318477319 cites W2049743082 @default.
• W2318477319 cites W2066337690 @default.
• W2318477319 cites W2079123938 @default.
• W2318477319 cites W2082665956 @default.
• W2318477319 cites W2088245562 @default.
• W2318477319 cites W2091823485 @default.
• W2318477319 cites W2094778272 @default.
• W2318477319 cites W2112047656 @default.
• W2318477319 cites W2113067867 @default.
• W2318477319 cites W2119259412 @default.
• W2318477319 cites W2121986537 @default.
• W2318477319 cites W2123781000 @default.
• W2318477319 cites W2154343997 @default.
• W2318477319 cites W4234143043 @default.
• W2318477319 doi "https://doi.org/10.1021/cb5001263" @default.
• W2318477319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4136710" @default.
• W2318477319 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24918547" @default.
• W2318477319 hasPublicationYear "2014" @default.
• W2318477319 type Work @default.
• W2318477319 sameAs 2318477319 @default.
• W2318477319 citedByCount "44" @default.
• W2318477319 countsByYear W23184773192015 @default.
• W2318477319 countsByYear W23184773192016 @default.
• W2318477319 countsByYear W23184773192017 @default.
• W2318477319 countsByYear W23184773192018 @default.
• W2318477319 countsByYear W23184773192019 @default.
• W2318477319 countsByYear W23184773192020 @default.
• W2318477319 countsByYear W23184773192021 @default.
• W2318477319 countsByYear W23184773192022 @default.
• W2318477319 countsByYear W23184773192023 @default.
• W2318477319 crossrefType "journal-article" @default.
• W2318477319 hasAuthorship W2318477319A5000584872 @default.
• W2318477319 hasAuthorship W2318477319A5003559845 @default.
• W2318477319 hasAuthorship W2318477319A5005370974 @default.
• W2318477319 hasAuthorship W2318477319A5005853846 @default.
• W2318477319 hasAuthorship W2318477319A5009402514 @default.
• W2318477319 hasAuthorship W2318477319A5019560977 @default.
• W2318477319 hasAuthorship W2318477319A5031836660 @default.
• W2318477319 hasAuthorship W2318477319A5056673744 @default.
• W2318477319 hasAuthorship W2318477319A5069804033 @default.
• W2318477319 hasAuthorship W2318477319A5080458286 @default.
• W2318477319 hasBestOaLocation W23184773191 @default.
• W2318477319 hasConcept C104292427 @default.
• W2318477319 hasConcept C104317684 @default.
• W2318477319 hasConcept C136764020 @default.
• W2318477319 hasConcept C203014093 @default.
• W2318477319 hasConcept C27740335 @default.
• W2318477319 hasConcept C2778048844 @default.
• W2318477319 hasConcept C2778371730 @default.
• W2318477319 hasConcept C2778675580 @default.
• W2318477319 hasConcept C41008148 @default.
• W2318477319 hasConcept C55493867 @default.
• W2318477319 hasConcept C71928629 @default.
• W2318477319 hasConcept C86803240 @default.
• W2318477319 hasConcept C95444343 @default.
• W2318477319 hasConceptScore W2318477319C104292427 @default.
• W2318477319 hasConceptScore W2318477319C104317684 @default.
• W2318477319 hasConceptScore W2318477319C136764020 @default.
• W2318477319 hasConceptScore W2318477319C203014093 @default.
• W2318477319 hasConceptScore W2318477319C27740335 @default.
• W2318477319 hasConceptScore W2318477319C2778048844 @default.
• W2318477319 hasConceptScore W2318477319C2778371730 @default.
• W2318477319 hasConceptScore W2318477319C2778675580 @default.
• W2318477319 hasConceptScore W2318477319C41008148 @default.
• W2318477319 hasConceptScore W2318477319C55493867 @default.

• next