{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:55:55Z","timestamp":1793354155714,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,8,14]]},"abstract":"<jats:p>\n                    Prion diseases in humans and animals are invariably fatal. Prions\n are composed of a disease-causing isoform (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ) of the\n normal host prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) and replicate by\n stimulating the conversion of PrP\n                    <jats:sup>C<\/jats:sup>\n                    into nascent\n PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . We report here that tricyclic derivatives of\n acridine and phenothiazine exhibit half-maximal inhibition of\n PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    formation at effective concentrations\n (EC\n                    <jats:sub>50<\/jats:sub>\n                    ) between 0.3 \u03bcM and 3 \u03bcM in cultured cells\n chronically infected with prions. The EC\n                    <jats:sub>50<\/jats:sub>\n                    for\n chlorpromazine was 3 \u03bcM, whereas quinacrine was 10 times more potent.\n A variety of 9-substituted, acridine-based analogues of quinacrine were\n synthesized, which demonstrated variable antiprion potencies similar to\n those of chlorpromazine and emphasized the importance of the side chain\n in mediating the inhibition of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    formation. Thus, our\n studies show that tricyclic compounds with an aliphatic side chain at\n the middle ring moiety constitute a new class of antiprion reagents.\n Because quinacrine and chlorpromazine have been used in humans for many\n years as antimalarial and antipsychotic drugs, respectively, and are\n known to pass the blood\u2013brain barrier, we suggest that they are\n immediate candidates for the treatment of Creutzfeldt\u2013Jakob disease\n and other prion diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.161274798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"9836-9841","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":571,"title":["Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease"],"prefix":"10.1073","volume":"98","author":[{"given":"Carsten","family":"Korth","sequence":"first","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of\r Cellular and Molecular Pharmacology,\r Biochemistry and Biophysics, Medicine, and\r Neurology, University of California, San Francisco, CA\r 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnaby C. H.","family":"May","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of\r Cellular and Molecular Pharmacology,\r Biochemistry and Biophysics, Medicine, and\r Neurology, University of California, San Francisco, CA\r 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred E.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of\r Cellular and Molecular Pharmacology,\r Biochemistry and Biophysics, Medicine, and\r Neurology, University of California, San Francisco, CA\r 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley B.","family":"Prusiner","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases and Departments of\r Cellular and Molecular Pharmacology,\r Biochemistry and Biophysics, Medicine, and\r Neurology, University of California, San Francisco, CA\r 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,8,14]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"509","volume-title":"Prion Biology and Diseases","author":"Gambetti P","year":"1999","unstructured":"P Gambetti, R B Peterson, P Parchi, S G Chen, S Capellari, L Goldfarb, R Gabizon, P Montagna, E Lugaresi, P Piccardo, B Ghetti Prion Biology and Diseases, ed S B Prusiner (Cold Spring Harbor Lab. 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