{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:06:25Z","timestamp":1765177585058},"reference-count":62,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative disorders that can be transmitted by natural infection or inoculation. TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans. The emergence of a variant form of CJD (vCJD), which has been associated with BSE, produced strong pressure to search for effective treatments with new drugs. Up to now, however, TSEs have proved incurable, although many efforts have been made both\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            to search for potent therapeutic and prophylactic compounds. For this purpose, we analyzed a compound library consisting of 10,000 compounds with a cell-based high-throughput screening assay dealing with scrapie-infected scrapie mouse brain and ScN\n            <jats:sub>2<\/jats:sub>\n            A cells and identified a new class of inhibitors consisting of 3,5-diphenylpyrazole (DPP) derivatives. The most effective DPP derivative showed half-maximal inhibition of PrP\n            <jats:sup>Sc<\/jats:sup>\n            formation at concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            ) of 0.6 and 1.2 \u03bcM, respectively. This compound was subsequently subjected to a number of animal experiments using scrapie-infected wild-type C57BL\/6 and transgenic Tga20 mice. The DPP derivative induced a significant increase of incubation time both in therapeutic and prophylactic experiments. The onset of the prion disease was delayed by 37 days after intraperitoneal and 42 days after oral application, respectively. In summary, we demonstrate a high\n            <jats:italic>in vitro<\/jats:italic>\n            efficiency of DPP derivatives against prion infections that was substantiated\n            <jats:italic>in vivo<\/jats:italic>\n            for one of these compounds. These results indicate that the novel class of DPP compounds should comprise excellent candidates for future therapeutic studies.\n          <\/jats:p>","DOI":"10.1128\/aac.00151-11","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T06:10:11Z","timestamp":1310451011000},"page":"4774-4781","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Diphenylpyrazole-Derived Compounds Increase Survival Time of Mice after Prion Infection"],"prefix":"10.1128","volume":"55","author":[{"given":"Fabienne","family":"Leidel","sequence":"first","affiliation":[{"name":"Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Eiden","sequence":"additional","affiliation":[{"name":"Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Geissen","sequence":"additional","affiliation":[{"name":"Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans A.","family":"Kretzschmar","sequence":"additional","affiliation":[{"name":"Institute for Neuropathology, Ludwig-Maximilians-Universit\u00e4t, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armin","family":"Giese","sequence":"additional","affiliation":[{"name":"Institute for Neuropathology, Ludwig-Maximilians-Universit\u00e4t, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hirschberger","sequence":"additional","affiliation":[{"name":"Arbeitsgruppe Theoretische Biophysik, Lehrstuhl f\u00fcr BioMolekulare Optik, Ludwig-Maximilians-Universit\u00e4t, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Tavan","sequence":"additional","affiliation":[{"name":"Arbeitsgruppe Theoretische Biophysik, Lehrstuhl f\u00fcr BioMolekulare Optik, Ludwig-Maximilians-Universit\u00e4t, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann M.","family":"Sch\u00e4tzl","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and of Veterinary Sciences, University of Wyoming, Laramie, Wyoming"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin H.","family":"Groschup","sequence":"additional","affiliation":[{"name":"Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"123","article-title":"What are the prospects for pharmacological treatment of prion disease?","volume":"57","author":"Adjou K. 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