{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:03:47Z","timestamp":1761541427196,"version":"3.41.2"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"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":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The new 2-aminomethylphenol, JPC-3210, has potent\n            <jats:italic>in vitro<\/jats:italic>\n            antimalarial activity against multidrug-resistant\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            lines, low cytotoxicity, and high\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy against murine malaria. Here we report on the pharmacokinetics of JPC-3210 in mice and monkeys and the results of\n            <jats:italic>in vitro<\/jats:italic>\n            screening assays, including the inhibition of cytochrome P450 (CYP450) isozymes. In mice, JPC-3210 was rapidly absorbed and had an extensive tissue distribution, with a brain tissue-to-plasma concentration ratio of about 5.4. JPC-3210 had a lengthy plasma elimination half-life of about 4.5 days in mice and 11.8 days in monkeys. JPC-3210 exhibited linear single-oral-dose pharmacokinetics across the dose range of 5 to 40 mg\/kg of body weight with high oral bioavailability (\u223c86%) in mice. Systemic blood exposure of JPC-3210 was 16.6% higher in\n            <jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>\n            -infected mice than in healthy mice.\n            <jats:italic>In vitro<\/jats:italic>\n            studies with mice and human hepatocytes revealed little metabolism and the high metabolic stability of JPC-3210. The abundance of human metabolites from oxidation and glucuronidation was 2.0% and 2.5%, respectively. CYP450 studies in human liver microsomes showed JPC-3210 to be an inhibitor of CYP2D6 and, to a lesser extent, CYP3A4 isozymes, suggesting the possibility of a metabolic drug-drug interaction with drugs that are metabolized by these isozymes.\n            <jats:italic>In vitro<\/jats:italic>\n            studies showed that JPC-3210 is highly protein bound to human plasma (97%). These desirable pharmacological findings of a lengthy blood elimination half-life, high oral bioavailability, and low metabolism as well as high\n            <jats:italic>in vivo<\/jats:italic>\n            potency have led the Medicines for Malaria Venture to select JPC-3210 (MMV892646) for further advanced preclinical development.\n          <\/jats:p>","DOI":"10.1128\/aac.01335-17","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T11:51:55Z","timestamp":1515498715000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Characterization of the Preclinical Pharmacology of the New 2-Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention"],"prefix":"10.1128","volume":"62","author":[{"given":"Geoffrey W.","family":"Birrell","sequence":"first","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute (AMI), Brisbane, Queensland, Australia"}],"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":"Guy A.","family":"Schiehser","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Anderson","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Princeton, New Jersey, USA"}],"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":"Pablo","family":"Morales","sequence":"additional","affiliation":[{"name":"Mannheimer Foundation, Inc., Homestead, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"MacKenzie","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute (AMI), Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"van Breda","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute (AMI), Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Chavchich","sequence":"additional","affiliation":[{"name":"Department of Drug Evaluation, Australian Army Malaria Institute (AMI), Brisbane, Queensland, Australia"}],"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 (AMI), 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 (AMI), 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\/4348b814-en"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15535"},{"key":"e_1_3_3_4_2","volume-title":"Guidelines for the treatment of malaria","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. 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