{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:29:02Z","timestamp":1791329342360,"version":"4.3.1"},"reference-count":44,"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            The apicoplast is an essential plastid organelle found in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            parasites which contains several clinically validated antimalarial-drug targets. A chemical rescue screen identified MMV-08138 from the \u201cMalaria Box\u201d library of growth-inhibitory antimalarial compounds as having specific activity against the apicoplast. MMV-08138 inhibition of blood-stage\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            growth is stereospecific and potent, with the most active diastereomer demonstrating a 50% effective concentration (EC\n            <jats:sub>50<\/jats:sub>\n            ) of 110 nM. Whole-genome sequencing of 3 drug-resistant parasite populations from two independent selections revealed E688Q and L244I mutations in\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            IspD, an enzyme in the MEP (methyl-\n            <jats:sc>d<\/jats:sc>\n            -erythritol-4-phosphate) isoprenoid precursor biosynthesis pathway in the apicoplast. The active diastereomer of MMV-08138 directly inhibited PfIspD activity\n            <jats:italic>in vitro<\/jats:italic>\n            with a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) of 7.0 nM. MMV-08138 is the first PfIspD inhibitor to be identified and, together with heterologously expressed PfIspD, provides the foundation for further development of this promising antimalarial drug candidate lead. Furthermore, this report validates the use of the apicoplast chemical rescue screen coupled with target elucidation as a discovery tool to identify specific apicoplast-targeting compounds with new mechanisms of action.\n          <\/jats:p>","DOI":"10.1128\/aac.03342-14","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T04:50:09Z","timestamp":1415076609000},"page":"356-364","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["A Chemical Rescue Screen Identifies a Plasmodium falciparum Apicoplast Inhibitor Targeting MEP Isoprenoid Precursor Biosynthesis"],"prefix":"10.1128","volume":"59","author":[{"given":"Wesley","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford Medical School, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Ebert","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Baska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford Medical School, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok H.","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"DeRisi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford Medical School, Stanford, California, USA"},{"name":"Department of Pathology, Stanford Medical School, Stanford, California, USA"},{"name":"Department of Microbiology and Immunology, Stanford Medical School, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World Malaria Report 2013","author":"WHO","year":"2013","unstructured":"WHO. 2013. World Malaria Report 2013. WHO, Geneva, Switzerland."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5305.1485"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003335107"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00394-06"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/BC20080202"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5433.1573"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-002-0770-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/424603"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/381785"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01448-06"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00018-12"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09099"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09107"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1cs15053g"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.495"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001138"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062906"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01500-13"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1534\/g3.113.005967"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-80"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_3_25_2","unstructured":"Reference deleted."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1794"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00808-06"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003375"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1039\/b903513c"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.259747"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol901961q"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.105"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201309557"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201102281"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1139\/g02-080"},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s004250100633","article-title":"An isoleucine-leucine substitution in chloroplastic acetyl-CoA carboxylase from green foxtail (Setaria viridis L. Beauv.) is responsible for resistance to the cyclohexanedione herbicide sethoxydim","volume":"214","author":"D\u00e9lye C","year":"2002","unstructured":"D\u00e9lye C, Wang T, Darmency H. 2002. An isoleucine-leucine substitution in chloroplastic acetyl-CoA carboxylase from green foxtail (Setaria viridis L. Beauv.) is responsible for resistance to the cyclohexanedione herbicide sethoxydim. Planta 214:421\u2013427.","journal-title":"Planta"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb300243w"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.08.012"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2253"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2252"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003522"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01270.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.11.001"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-187"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.9.2889-2894.2002"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03342-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03342-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:56:54Z","timestamp":1645484214000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.03342-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1128\/AAC.03342-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.03342-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"2014-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}