{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T02:40:57Z","timestamp":1772505657940,"version":"3.50.1"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"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":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            4-(\n            <jats:italic>tert<\/jats:italic>\n            -Butyl)-2-((\n            <jats:italic>tert<\/jats:italic>\n            -butylamino)methyl)-6-(6-(trifluoromethyl)pyridin-3-yl)-phenol (JPC-2997) is a new aminomethylphenol compound that is highly active\n            <jats:italic>in vitro<\/jats:italic>\n            against the chloroquine-sensitive D6, the chloroquine-resistant W2, and the multidrug-resistant TM90-C2B\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            lines, with 50% inhibitory concentrations (IC\n            <jats:sub>50s<\/jats:sub>\n            ) ranging from 7 nM to 34 nM. JPC-2997 is &gt;2,500 times less cytotoxic (IC\n            <jats:sub>50<\/jats:sub>\n            s &gt; 35 \u03bcM) to human (HepG2 and HEK293) and rodent (BHK) cell lines than the D6 parasite line. In comparison to the chemically related WR-194,965, a drug that had advanced to clinical studies, JPC-2997 was 2-fold more active\n            <jats:italic>in vitro<\/jats:italic>\n            against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            lines and 3-fold less cytotoxic. The compound possesses potent\n            <jats:italic>in vivo<\/jats:italic>\n            suppression activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium berghei<\/jats:named-content>\n            , with a 50% effective dose (ED\n            <jats:sub>50<\/jats:sub>\n            ) of 0.5 mg\/kg of body weight\/day following oral dosing in the Peters 4-day test. The radical curative dose of JPC-2997 was remarkably low, at a total dose of 24 mg\/kg, using the modified Thompson test. JPC-2997 was effective in curing three\n            <jats:italic>Aotus<\/jats:italic>\n            monkeys infected with a chloroquine- and pyrimethamine-resistant strain of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium vivax<\/jats:named-content>\n            at a dose of 20 mg\/kg daily for 3 days. At the doses administered, JPC-2997 appeared to be well tolerated in mice and monkeys. Preliminary studies of JPC-2997 in mice show linear pharmacokinetics over the range 2.5 to 40 mg\/kg, a low clearance of 0.22 liters\/h\/kg, a volume of distribution of 15.6 liters\/kg, and an elimination half-life of 49.8 h. The high\n            <jats:italic>in vivo<\/jats:italic>\n            potency data and lengthy elimination half-life of JPC-2997 suggest that it is worthy of further preclinical assessment as a partner drug.\n          <\/jats:p>","DOI":"10.1128\/aac.03762-14","type":"journal-article","created":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T02:43:11Z","timestamp":1413859391000},"page":"170-177","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["JPC-2997, a New Aminomethylphenol with High\n            <i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Antimalarial Activities against Blood Stages of Plasmodium"],"prefix":"10.1128","volume":"59","author":[{"given":"Geoffrey W.","family":"Birrell","sequence":"first","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Chavchich","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arba L.","family":"Ager","sequence":"additional","affiliation":[{"name":"University of Miami, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong-Ming","family":"Shieh","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin D.","family":"Heffernan","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter E.","family":"Krasucki","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt W.","family":"Saionz","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacek","family":"Terpinski","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy A.","family":"Schiehser","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura R.","family":"Jacobus","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Dennis","family":"Shanks","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Jacobus","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Edstein","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute, Enoggera, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.30875\/ac42f7b8-en"},{"key":"e_1_3_3_3_2","volume-title":"World Health Organization","author":"World Health Organization","year":"2010","unstructured":"World Health Organization. 2010. 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