FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4289638467> ?p ?o ?g. }

• W4289638467 abstract "The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include Toxoplasma gondii, Plasmodium, and Cryptosporidium spp., which infect humans and animals and cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. We use a drug repurposing strategy and identify altiratinib, a compound originally developed to treat glioblastoma, as a promising drug candidate with broad spectrum activity against apicomplexans. Altiratinib is parasiticidal and blocks the development of intracellular zoites in the nanomolar range and with a high selectivity index when used against T. gondii. We have identified TgPRP4K of T. gondii as the primary target of altiratinib using genetic target deconvolution, which highlighted key residues within the kinase catalytic site that conferred drug resistance when mutated. We have further elucidated the molecular basis of the inhibitory mechanism and species selectivity of altiratinib for TgPRP4K and for its Plasmodium falciparum counterpart, PfCLK3. Our data identified structural features critical for binding of the other PfCLK3 inhibitor, TCMDC-135051. Consistent with the splicing control activity of this kinase family, we have shown that altiratinib can cause global disruption of splicing, primarily through intron retention in both T. gondii and P. falciparum. Thus, our data establish parasitic PRP4K/CLK3 as a potential pan-apicomplexan target whose repertoire of inhibitors can be expanded by the addition of altiratinib." @default.
• W4289638467 created "2022-08-03" @default.
• W4289638467 creator A5016121410 @default.
• W4289638467 creator A5028161034 @default.
• W4289638467 creator A5037901255 @default.
• W4289638467 creator A5039009013 @default.
• W4289638467 creator A5040984498 @default.
• W4289638467 creator A5041453244 @default.
• W4289638467 creator A5051955080 @default.
• W4289638467 creator A5059545052 @default.
• W4289638467 creator A5064992009 @default.
• W4289638467 creator A5069199417 @default.
• W4289638467 creator A5073284807 @default.
• W4289638467 creator A5080798906 @default.
• W4289638467 creator A5085954072 @default.
• W4289638467 date "2022-08-03" @default.
• W4289638467 modified "2023-10-16" @default.
• W4289638467 title "Altiratinib blocks <i>Toxoplasma gondii</i> and <i>Plasmodium falciparum</i> development by selectively targeting a spliceosome kinase" @default.
• W4289638467 cites W1488917404 @default.
• W4289638467 cites W1712461720 @default.
• W4289638467 cites W1893111942 @default.
• W4289638467 cites W1928288000 @default.
• W4289638467 cites W1951334236 @default.
• W4289638467 cites W1969503178 @default.
• W4289638467 cites W1980432902 @default.
• W4289638467 cites W2002392594 @default.
• W4289638467 cites W2015810688 @default.
• W4289638467 cites W2056017147 @default.
• W4289638467 cites W2057368600 @default.
• W4289638467 cites W2064455466 @default.
• W4289638467 cites W2087764699 @default.
• W4289638467 cites W2092298531 @default.
• W4289638467 cites W2110905563 @default.
• W4289638467 cites W2111109297 @default.
• W4289638467 cites W2111782650 @default.
• W4289638467 cites W2120887723 @default.
• W4289638467 cites W2127130852 @default.
• W4289638467 cites W2144081223 @default.
• W4289638467 cites W2156189508 @default.
• W4289638467 cites W2163341755 @default.
• W4289638467 cites W2225873253 @default.
• W4289638467 cites W2305558625 @default.
• W4289638467 cites W2432815617 @default.
• W4289638467 cites W2511428910 @default.
• W4289638467 cites W2514790758 @default.
• W4289638467 cites W2744206279 @default.
• W4289638467 cites W2792649904 @default.
• W4289638467 cites W2802130188 @default.
• W4289638467 cites W2808348004 @default.
• W4289638467 cites W2889776706 @default.
• W4289638467 cites W2939469771 @default.
• W4289638467 cites W2970919192 @default.
• W4289638467 cites W2991428742 @default.
• W4289638467 cites W3008516049 @default.
• W4289638467 cites W3011428862 @default.
• W4289638467 cites W3046052568 @default.
• W4289638467 cites W3046078147 @default.
• W4289638467 cites W3107488437 @default.
• W4289638467 cites W3177287793 @default.
• W4289638467 cites W3177828909 @default.
• W4289638467 cites W3180489412 @default.
• W4289638467 cites W4211140781 @default.
• W4289638467 cites W4248872320 @default.
• W4289638467 cites W4281790889 @default.
• W4289638467 doi "https://doi.org/10.1126/scitranslmed.abn3231" @default.
• W4289638467 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35921477" @default.
• W4289638467 hasPublicationYear "2022" @default.
• W4289638467 type Work @default.
• W4289638467 citedByCount "6" @default.
• W4289638467 countsByYear W42896384672023 @default.
• W4289638467 crossrefType "journal-article" @default.
• W4289638467 hasAuthorship W4289638467A5016121410 @default.
• W4289638467 hasAuthorship W4289638467A5028161034 @default.
• W4289638467 hasAuthorship W4289638467A5037901255 @default.
• W4289638467 hasAuthorship W4289638467A5039009013 @default.
• W4289638467 hasAuthorship W4289638467A5040984498 @default.
• W4289638467 hasAuthorship W4289638467A5041453244 @default.
• W4289638467 hasAuthorship W4289638467A5051955080 @default.
• W4289638467 hasAuthorship W4289638467A5059545052 @default.
• W4289638467 hasAuthorship W4289638467A5064992009 @default.
• W4289638467 hasAuthorship W4289638467A5069199417 @default.
• W4289638467 hasAuthorship W4289638467A5073284807 @default.
• W4289638467 hasAuthorship W4289638467A5080798906 @default.
• W4289638467 hasAuthorship W4289638467A5085954072 @default.
• W4289638467 hasBestOaLocation W42896384672 @default.
• W4289638467 hasConcept C104317684 @default.
• W4289638467 hasConcept C136764020 @default.
• W4289638467 hasConcept C153726182 @default.
• W4289638467 hasConcept C159047783 @default.
• W4289638467 hasConcept C159654299 @default.
• W4289638467 hasConcept C184235292 @default.
• W4289638467 hasConcept C203014093 @default.
• W4289638467 hasConcept C2775855988 @default.
• W4289638467 hasConcept C2778048844 @default.
• W4289638467 hasConcept C2778128430 @default.
• W4289638467 hasConcept C2778371730 @default.
• W4289638467 hasConcept C2778675580 @default.
• W4289638467 hasConcept C2778877831 @default.
• W4289638467 hasConcept C2781023229 @default.
• W4289638467 hasConcept C41008148 @default.

• next