{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:41:58Z","timestamp":1792687318245,"version":"4.5.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T00:00:00Z","timestamp":1444003200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Drug Discov"],"published-print":{"date-parts":[[2015,11]]},"DOI":"10.1038\/nrd4683","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T01:11:41Z","timestamp":1444007501000},"page":"751-758","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":576,"title":["Hit and lead criteria in drug discovery for infectious diseases of the developing world"],"prefix":"10.1038","volume":"14","author":[{"given":"Kei","family":"Katsuno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy N.","family":"Burrows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob Hooft","family":"van Huijsduijnen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takushi","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Mowbray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Schmatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Warner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. T.","family":"Slingsby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,10,5]]},"reference":[{"key":"BFnrd4683_CR1","unstructured":"World Health Organization. Antimicrobial resistance: global report on surveillance 2014 (WHO, 2014)."},{"key":"BFnrd4683_CR2","first-page":"2","volume":"1","author":"EA Martis","year":"2011","unstructured":"Martis, E. A., Radhakrishnan, R. & Badve, R. R. High-throughput screening: the hits and leads of drug discovery \u2014 an overview. J. Appl. Pharma. Sci. 1, 2\u201310 (2011).","journal-title":"J. Appl. Pharma. Sci."},{"key":"BFnrd4683_CR3","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.drudis.2012.05.007","volume":"17","author":"I Khanna","year":"2012","unstructured":"Khanna, I. Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discov. Today 17, 1088\u20131102 (2012).","journal-title":"Drug Discov. Today"},{"key":"BFnrd4683_CR4","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/nrd2144","volume":"5","author":"S Nwaka","year":"2006","unstructured":"Nwaka, S. & Hudson, A. Innovative lead discovery strategies for tropical diseases. Nat. Rev. Drug Discov. 5, 941\u2013955 (2006).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR5","doi-asserted-by":"publisher","first-page":"e440","DOI":"10.1371\/journal.pntd.0000440","volume":"3","author":"S Nwaka","year":"2009","unstructured":"Nwaka, S. et al. Advancing drug innovation for neglected diseases-criteria for lead progression. PLoS Negl Trop. Dis. 3, e440 (2009).","journal-title":"PLoS Negl Trop. Dis."},{"key":"BFnrd4683_CR6","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/1475-2875-12-187","volume":"12","author":"JN Burrows","year":"2013","unstructured":"Burrows, J. N., Hooft van Huijsduijnen, R., M\u00f6hrle, J. J., Oeuvray, C. & Wells, T. N. C. Designing the next generation of medicines for malaria control and eradication. Malar. J. 12, 187 (2013).","journal-title":"Malar. J."},{"key":"BFnrd4683_CR7","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/clpt.2012.236","volume":"93","author":"DC Swinney","year":"2013","unstructured":"Swinney, D. C. Phenotypic versus target-based drug discovery for first-in-class medicines. Clin. Pharmacol. Ther. 93, 299\u2013301 (2013).","journal-title":"Clin. Pharmacol. Ther."},{"key":"BFnrd4683_CR8","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrd4336","volume":"13","author":"J Eder","year":"2014","unstructured":"Eder, J., Sedrani, R. & Wiesmann, C. The discovery of first-in-class drugs: origins and evolution. Nat. Rev. Drug Discov. 13, 577\u2013587 (2014).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR9","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nrd2201","volume":"6","author":"DJ Payne","year":"2007","unstructured":"Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6, 29\u201340 (2007).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR10","doi-asserted-by":"publisher","first-page":"5381","DOI":"10.1021\/jm500481t","volume":"57","author":"X Deng","year":"2014","unstructured":"Deng, X. et al. Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors. J. Med. Chem. 57, 5381\u20135394 (2014).","journal-title":"J. Med. Chem."},{"key":"BFnrd4683_CR11","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1128\/CMR.15.3.355-364.2002","volume":"15","author":"FL Schuster","year":"2002","unstructured":"Schuster, F. L. Cultivation of Plasmodium spp. Clin. Microbiol. Rev. 15, 355\u2013364 (2002).","journal-title":"Clin. Microbiol. Rev."},{"issue":"Suppl. 3","key":"BFnrd4683_CR12","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/1475-2875-9-S3-S6","volume":"9","author":"BK Mutai","year":"2010","unstructured":"Mutai, B. K. & Waitumbi, J. N. Apoptosis stalks Plasmodium falciparum maintained in continuous culture condition. Malar J. 9 (Suppl. 3), S6 (2010).","journal-title":"Malar J."},{"key":"BFnrd4683_CR13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1177\/1087057114550585","volume":"20","author":"E Chatelain","year":"2015","unstructured":"Chatelain, E. Chagas disease drug discovery: toward a new era. J. Biomol. Screen 20, 22\u201335 (2015).","journal-title":"J. Biomol. Screen"},{"key":"BFnrd4683_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrd4573","volume":"14","author":"TNC Wells","year":"2015","unstructured":"Wells, T. N. C., Hooft van Huijsduijnen, R. & Van Voorhis, W. C. Malaria medicines: a glass half full? Nat. Rev. Drug Discov. 14, 1\u201318 (2015).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR15","doi-asserted-by":"publisher","first-page":"193","DOI":"10.4269\/ajtmh.2007.77.193","volume":"77","author":"A Bosman","year":"2007","unstructured":"Bosman, A. & Mendis, K. N. A major transition in malaria treatment: the adoption and deployment of artemisinin-based combination therapies. Am. J. Trop. Med. Hyg. 77, 193\u2013197 (2007).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"BFnrd4683_CR16","doi-asserted-by":"publisher","first-page":"597","DOI":"10.2147\/TCRM.S37743","volume":"10","author":"E Leibert","year":"2014","unstructured":"Leibert, E., Danckers, M. & Rom, W. N. New drugs to treat multidrug-resistant tuberculosis: the case for bedaquiline. Ther. Clin. Risk Manag. 10, 597\u2013602 (2014).","journal-title":"Ther. Clin. Risk Manag."},{"key":"BFnrd4683_CR17","doi-asserted-by":"publisher","first-page":"222","DOI":"10.4103\/0976-500X.136121","volume":"5","author":"AS Xavier","year":"2014","unstructured":"Xavier, A. S. & Lakshmanan, M. Delamanid: a new armor in combating drug-resistant tuberculosis. J. Pharmacol. Pharmacother. 5, 222\u2013224 (2014).","journal-title":"J. Pharmacol. Pharmacother."},{"key":"BFnrd4683_CR18","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S1359-6446(05)03700-1","volume":"11","author":"T Wunberg","year":"2006","unstructured":"Wunberg, T. et al. Improving the hit-to-lead process: data-driven assessment of drug-like and lead-like screening hits. Drug Discov. Today 11, 175\u2013180 (2006).","journal-title":"Drug Discov. Today"},{"key":"BFnrd4683_CR19","volume-title":"Assay Guidance Manual","author":"M Hughes","year":"2012","unstructured":"Hughes, M. et al. Early drug discovery and development guidelines: for academic researchers, collaborators, and start-up companies. Assay Guidance Manual [online] , (2012)."},{"key":"BFnrd4683_CR20","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","volume":"505","author":"F Ariey","year":"2014","unstructured":"Ariey, F. et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505, 50\u201355 (2014).","journal-title":"Nature"},{"key":"BFnrd4683_CR21","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1056\/NEJMoa1314981","volume":"371","author":"EA Ashley","year":"2014","unstructured":"Ashley, E. A. et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med. 371, 411\u2013423 (2014).","journal-title":"N. Engl. J. Med."},{"key":"BFnrd4683_CR22","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/nature14387","volume":"520","author":"J Burrows","year":"2015","unstructured":"Burrows, J. Microbiology: malaria runs rings round artemisinin. Nature 520, 628\u2013630 (2015).","journal-title":"Nature"},{"key":"BFnrd4683_CR23","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/nature14412","volume":"520","author":"A Mbengue","year":"2015","unstructured":"Mbengue, A. et al. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520, 683\u2013687 (2015).","journal-title":"Nature"},{"key":"BFnrd4683_CR24","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/7355_2011_14","volume-title":"Third World Diseases","author":"JN Burrows","year":"2011","unstructured":"Burrows, J. N. & Waterson, D. in Third World Diseases (ed. Elliot, R. L.) 125\u2013180 (Springer, 2011)."},{"key":"BFnrd4683_CR25","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1038\/nature09107","volume":"465","author":"FJ Gamo","year":"2010","unstructured":"Gamo, F. J. et al. Thousands of chemical starting points for antimalarial lead identification. Nature 465, 305\u2013310 (2010).","journal-title":"Nature"},{"key":"BFnrd4683_CR26","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/nature09099","volume":"465","author":"WA Guiguemde","year":"2010","unstructured":"Guiguemde, W. A. et al. Chemical genetics of Plasmodium falciparum. Nature 465, 311\u2013315 (2010).","journal-title":"Nature"},{"key":"BFnrd4683_CR27","doi-asserted-by":"publisher","first-page":"9059","DOI":"10.1073\/pnas.0802982105","volume":"105","author":"D Plouffe","year":"2008","unstructured":"Plouffe, D. et al. In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc. Natl Acad. Sci. USA 105, 9059\u20139064 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrd4683_CR28","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1126\/science.1211936","volume":"334","author":"S Meister","year":"2011","unstructured":"Meister, S. et al. Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery. Science 334, 1372\u20131377 (2011).","journal-title":"Science"},{"key":"BFnrd4683_CR29","doi-asserted-by":"publisher","first-page":"e2252","DOI":"10.1371\/journal.pone.0002252","volume":"3","author":"I Angulo-Barturen","year":"2008","unstructured":"Angulo-Barturen, I. et al. A murine model of falciparum-malaria by in vivo selection of competent strains in non-myelodepleted mice engrafted with human erythrocytes. PLoS ONE 3, e2252 (2008).","journal-title":"PLoS ONE"},{"key":"BFnrd4683_CR30","doi-asserted-by":"publisher","first-page":"177ra37","DOI":"10.1126\/scitranslmed.3005029","volume":"5","author":"A Nilsen","year":"2013","unstructured":"Nilsen, A. et al. Quinolone-3-diarylethers: a new class of antimalarial drug. Sci. Transl. Med. 5, 177ra37 (2013).","journal-title":"Sci. Transl. Med."},{"key":"BFnrd4683_CR31","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1186\/s13059-014-0544-6","volume":"15","author":"EA Winzeler","year":"2014","unstructured":"Winzeler, E. A. & Manary, M. J. Drug resistance genomics of the antimalarial drug artemisinin. Genome Biol. 15, 544 (2014).","journal-title":"Genome Biol."},{"key":"BFnrd4683_CR32","doi-asserted-by":"publisher","first-page":"490","DOI":"10.3201\/eid2103.140898","volume":"21","author":"R Isozumi","year":"2015","unstructured":"Isozumi, R. et al. Novel mutations in K13 propeller gene of artemisinin-resistant Plasmodium falciparum. Emerg. Infect. Dis. 21, 490\u2013492 (2015).","journal-title":"Emerg. Infect. Dis."},{"key":"BFnrd4683_CR33","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S1473-3099(15)70032-0","volume":"15","author":"KM Tun","year":"2015","unstructured":"Tun, K. M. et al. Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker. Lancet Infect. Dis. 15, 415\u2013421 (2015).","journal-title":"Lancet Infect. Dis."},{"key":"BFnrd4683_CR34","doi-asserted-by":"publisher","first-page":"e18162","DOI":"10.1371\/journal.pone.0018162","volume":"6","author":"L Dembele","year":"2011","unstructured":"Dembele, L. et al. Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery. PLoS ONE 6, e18162 (2011).","journal-title":"PLoS ONE"},{"key":"BFnrd4683_CR35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/1475-2875-11-70","volume":"11","author":"RE Sinden","year":"2012","unstructured":"Sinden, R. E., Carter, R., Drakeley, C. & Leroy, D. The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies. Malar J. 11, 70 (2012).","journal-title":"Malar J."},{"key":"BFnrd4683_CR36","unstructured":"World Health Organization. Global tuberculosis report 2014. WHO [online] , (2014)."},{"key":"BFnrd4683_CR37","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/JCM.36.2.362-366.1998","volume":"36","author":"SG Franzblau","year":"1998","unstructured":"Franzblau, S. G. et al. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J. Clin. Microbiol. 36, 362\u2013366 (1998).","journal-title":"J. Clin. Microbiol."},{"key":"BFnrd4683_CR38","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1128\/AAC.00055-06","volume":"51","author":"SH Cho","year":"2007","unstructured":"Cho, S. H. et al. Low-oxygen-recovery assay for high-throughput screening of compounds against nonreplicating Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 51, 1380\u20131385 (2007).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnrd4683_CR39","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1021\/cb2004884","volume":"7","author":"PA Mak","year":"2012","unstructured":"Mak, P. A. et al. A high-throughput screen to identify inhibitors of ATP homeostasis in non-replicating Mycobacterium tuberculosis. ACS Chem. Biol. 7, 1190\u20131197 (2012).","journal-title":"ACS Chem. Biol."},{"key":"BFnrd4683_CR40","first-page":"247","volume":"54","author":"LG Wayne","year":"2001","unstructured":"Wayne, L. G. In vitro model of hypoxically induced nonreplicating persistence of Mycobacterium tuberculosis. Methods Mol. Med. 54, 247\u2013269 (2001).","journal-title":"Methods Mol. Med."},{"key":"BFnrd4683_CR41","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1093\/jac\/dku457","volume":"70","author":"SB Lakshminarayana","year":"2015","unstructured":"Lakshminarayana, S. B. et al. Comprehensive physicochemical, pharmacokinetic and activity profiling of anti-TB agents. J. Antimicrob. Chemother. 70, 857\u2013867 (2015).","journal-title":"J. Antimicrob. Chemother."},{"key":"BFnrd4683_CR42","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.mib.2006.12.007","volume":"10","author":"N Dhar","year":"2007","unstructured":"Dhar, N. & McKinney, J. D. Microbial phenotypic heterogeneity and antibiotic tolerance. Curr. Opin. Microbiol. 10, 30\u201338 (2007).","journal-title":"Curr. Opin. Microbiol."},{"key":"BFnrd4683_CR43","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.2741\/1293","volume":"9","author":"DA Mitchison","year":"2004","unstructured":"Mitchison, D. A. The search for new sterilizing anti-tuberculosis drugs. Front. Biosci. 9, 1059\u20131072 (2004).","journal-title":"Front. Biosci."},{"key":"BFnrd4683_CR44","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.tube.2012.07.003","volume":"92","author":"SG Franzblau","year":"2012","unstructured":"Franzblau, S. G. et al. Comprehensive analysis of methods used for the evaluation of compounds against Mycobacterium tuberculosis. Tuberculosis (Edinb.) 92, 453\u2013488 (2012).","journal-title":"Tuberculosis (Edinb.)"},{"key":"BFnrd4683_CR45","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1128\/AAC.03705-14","volume":"59","author":"M Silva-Miranda","year":"2015","unstructured":"Silva-Miranda, M. et al. High-content screening technology combined with a human granuloma model as a new approach to evaluate the activities of drugs against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 59, 693\u2013697 (2015).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnrd4683_CR46","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1038\/nm.3262","volume":"19","author":"K Pethe","year":"2013","unstructured":"Pethe, K. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat. Med. 19, 1157\u20131160 (2013).","journal-title":"Nat. Med."},{"key":"BFnrd4683_CR47","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1038\/ni.1781","volume":"10","author":"DG Russell","year":"2009","unstructured":"Russell, D. G., Cardona, P. J., Kim, M. J., Allain, S. & Altare, F. Foamy macrophages and the progression of the human tuberculosis granuloma. Nat. Immunol. 10, 943\u2013948 (2009).","journal-title":"Nat. Immunol."},{"key":"BFnrd4683_CR48","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1093\/infdis\/jir786","volume":"205","author":"J Harper","year":"2012","unstructured":"Harper, J. et al. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. J. Infect. Dis. 205, 595\u2013602 (2012).","journal-title":"J. Infect. Dis."},{"key":"BFnrd4683_CR49","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1073\/pnas.1424563112","volume":"112","author":"M Datta","year":"2015","unstructured":"Datta, M. et al. Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery. Proc. Natl Acad. Sci. USA 112, 1827\u20131832 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrd4683_CR50","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/imr.12255","volume":"264","author":"TR Hawn","year":"2015","unstructured":"Hawn, T. R., Shah, J. A. & Kalman, D. New tricks for old dogs: countering antibiotic resistance in tuberculosis with host-directed therapeutics. Immunol. Rev. 264, 344\u2013362 (2015).","journal-title":"Immunol. Rev."},{"key":"BFnrd4683_CR51","doi-asserted-by":"publisher","first-page":"151","DOI":"10.4103\/0974-777X.62883","volume":"2","author":"EM Moore","year":"2010","unstructured":"Moore, E. M. & Lockwood, D. N. Treatment of visceral leishmaniasis. J. Glob. Infect. Dis. 2, 151\u2013158 (2010).","journal-title":"J. Glob. Infect. Dis."},{"key":"BFnrd4683_CR52","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1517\/14656566.2015.973850","volume":"16","author":"S Sundar","year":"2014","unstructured":"Sundar, S. & Chakravarty, J. An update on pharmacotherapy for leishmaniasis. Expert Opin. Pharmacother. 16, 237\u2013252 (2014).","journal-title":"Expert Opin. Pharmacother."},{"key":"BFnrd4683_CR53","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1056\/NEJMoa1313122","volume":"370","author":"I Molina","year":"2014","unstructured":"Molina, I. et al. Randomized trial of posaconazole and benznidazole for chronic Chagas' disease. N. Engl. J. Med. 370, 1899\u20131908 (2014).","journal-title":"N. Engl. J. Med."},{"key":"BFnrd4683_CR54","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1128\/AAC.02398-12","volume":"57","author":"M De Rycker","year":"2013","unstructured":"De Rycker, M. et al. Comparison of a high-throughput high-content intracellular Leishmania donovani assay with an axenic amastigote assay. Antimicrob. Agents Chemother. 57, 2913\u20132922 (2013).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnrd4683_CR55","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.4155\/fmc.13.139","volume":"5","author":"M Keenan","year":"2013","unstructured":"Keenan, M. et al. Selection and optimization of hits from a high-throughput phenotypic screen against Trypanosoma cruzi. Future Med. Chem. 5, 1733\u20131752 (2013).","journal-title":"Future Med. Chem."},{"key":"BFnrd4683_CR56","doi-asserted-by":"publisher","first-page":"8771","DOI":"10.1038\/srep08771","volume":"5","author":"I Pena","year":"2015","unstructured":"Pena, I. et al. New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource. Sci. Rep. 5, 8771 (2015).","journal-title":"Sci. Rep."},{"key":"BFnrd4683_CR57","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1017\/S003118201300142X","volume":"141","author":"R Don","year":"2014","unstructured":"Don, R. & Ioset, J. R. Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections. Parasitology 141, 140\u2013146 (2014).","journal-title":"Parasitology"},{"key":"BFnrd4683_CR58","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","volume":"46","author":"CA Lipinski","year":"2001","unstructured":"Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3\u201326 (2001).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"BFnrd4683_CR59","doi-asserted-by":"publisher","first-page":"7719","DOI":"10.1021\/jm400362b","volume":"56","author":"IH Gilbert","year":"2013","unstructured":"Gilbert, I. H. Drug discovery for neglected diseases: molecular target-based and phenotypic approaches. J. Med. Chem. 56, 7719\u20137726 (2013).","journal-title":"J. Med. Chem."},{"key":"BFnrd4683_CR60","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.2174\/13895575113136660097","volume":"13","author":"MT Ansari","year":"2013","unstructured":"Ansari, M. T. et al. Malaria and artemisinin derivatives: an updated review. Mini Rev. Med. Chem. 13, 1879\u20131902 (2013).","journal-title":"Mini Rev. Med. Chem."},{"key":"BFnrd4683_CR61","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.reprotox.2009.05.002","volume":"28","author":"RL Clark","year":"2009","unstructured":"Clark, R. L. Embryotoxicity of the artemisinin antimalarials and potential consequences for use in women in the first trimester. Reprod. Toxicol. 28, 285\u2013296 (2009).","journal-title":"Reprod. Toxicol."},{"key":"BFnrd4683_CR62","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1086\/502658","volume":"42","author":"S Toovey","year":"2006","unstructured":"Toovey, S. Safety of artemisinin antimalarials. Clin. Infect. Dis. 42, 1214\u20131215 (2006).","journal-title":"Clin. Infect. Dis."},{"key":"BFnrd4683_CR63","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1124\/jpet.106.109058","volume":"319","author":"S Braselmann","year":"2006","unstructured":"Braselmann, S. et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J. Pharmacol. Exp. Ther. 319, 998\u20131008 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"BFnrd4683_CR64","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1021\/np030498t","volume":"67","author":"NH Oberlies","year":"2004","unstructured":"Oberlies, N. H. & Kroll, D. J. Camptothecin and taxol: historic achievements in natural products research. J. Nat. Prod. 67, 129\u2013135 (2004).","journal-title":"J. Nat. Prod."},{"key":"BFnrd4683_CR65","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.drudis.2006.12.008","volume":"12","author":"CK Tsang","year":"2007","unstructured":"Tsang, C. K., Qi, H., Liu, L. F. & Zheng, X. F. Targeting mammalian target of rapamycin (mTOR) for health and diseases. Drug Discov. Today 12, 112\u2013124 (2007).","journal-title":"Drug Discov. Today"},{"key":"BFnrd4683_CR66","first-page":"433","volume":"114","author":"JF Borel","year":"2002","unstructured":"Borel, J. F. History of the discovery of cyclosporin and of its early pharmacological development. Wien Klin. Wochenschr. 114, 433\u2013437 (2002).","journal-title":"Wien Klin. Wochenschr."},{"key":"BFnrd4683_CR67","doi-asserted-by":"publisher","first-page":"e184","DOI":"10.1016\/S2214-109X(13)70055-X","volume":"1","author":"BT Slingsby","year":"2013","unstructured":"Slingsby, B. T. & Kurokawa, K. The Global Health Innovative Technology (GHIT) fund: financing medical innovations for neglected populations. Lancet Glob. Health 1, e184\u2013185 (2013).","journal-title":"Lancet Glob. Health"},{"key":"BFnrd4683_CR68","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1038\/nrd4197","volume":"12","author":"D Holmes","year":"2013","unstructured":"Holmes, D. The GHIT fund shows its cards. Nat. Rev. Drug Discov. 12, 894 (2013).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR69","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2183\/pjab.87.13","volume":"87","author":"A Crump","year":"2011","unstructured":"Crump, A. & Omura, S. Ivermectin, 'wonder drug' from Japan: the human use perspective. Proc. Jpn Acad., Ser. B 87, 13\u201328 (2011).","journal-title":"Proc. Jpn Acad., Ser. B"},{"key":"BFnrd4683_CR70","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.pt.2007.03.005","volume":"23","author":"K Kita","year":"2007","unstructured":"Kita, K., Shiomi, K. & Omura, S. Advances in drug discovery and biochemical studies. Trends Parasitol. 23, 223\u2013229 (2007).","journal-title":"Trends Parasitol."},{"key":"BFnrd4683_CR71","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/nrmicro1048","volume":"2","author":"S Omura","year":"2004","unstructured":"Omura, S. & Crump, A. The life and times of ivermectin - a success story. Nat. Rev. Microbiol. 2, 984\u2013989 (2004).","journal-title":"Nat. Rev. Microbiol."},{"key":"BFnrd4683_CR72","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1021\/np2000528","volume":"74","author":"CR Strader","year":"2011","unstructured":"Strader, C. R., Pearce, C. J. & Oberlies, N. H. Fingolimod (FTY720): a recently approved multiple sclerosis drug based on a fungal secondary metabolite. J. Nat. Prod. 74, 900\u2013907 (2011).","journal-title":"J. Nat. Prod."},{"key":"BFnrd4683_CR73","doi-asserted-by":"publisher","first-page":"484","DOI":"10.2183\/pjab.86.484","volume":"86","author":"A Endo","year":"2010","unstructured":"Endo, A. A historical perspective on the discovery of statins. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 86, 484\u2013493 (2010).","journal-title":"Proc. Jpn Acad. Ser. B Phys. Biol. Sci."},{"key":"BFnrd4683_CR74","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/nrd1112","volume":"2","author":"JA Tobert","year":"2003","unstructured":"Tobert, J. A. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat. Rev. Drug Discov. 2, 517\u2013526 (2003).","journal-title":"Nat. Rev. Drug Discov."},{"key":"BFnrd4683_CR75","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1021\/jm901137j","volume":"53","author":"JB Baell","year":"2010","unstructured":"Baell, J. B. & Holloway, G. A. New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem. 53, 2719\u20132740 (2010).","journal-title":"J. Med. Chem."},{"key":"BFnrd4683_CR76","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1021\/jm010533y","volume":"45","author":"SL McGovern","year":"2002","unstructured":"McGovern, S. L., Caselli, E., Grigorieff, N. & Shoichet, B. K. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45, 1712\u20131722 (2002).","journal-title":"J. Med. Chem."},{"key":"BFnrd4683_CR77","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/513481a","volume":"513","author":"J Baell","year":"2014","unstructured":"Baell, J. & Walters, M. A. Chemistry: chemical con artists foil drug discovery. Nature 513, 481\u2013483 (2014).","journal-title":"Nature"},{"key":"BFnrd4683_CR78","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.4155\/fmc.11.91","volume":"3","author":"JN Burrows","year":"2011","unstructured":"Burrows, J. N., Leroy, D., Lotharius, J. & Waterson, D. Challenges in antimalarial drug discovery. Future Med. Chem. 3, 1401\u20131412 (2011).","journal-title":"Future Med. Chem."},{"key":"BFnrd4683_CR79","doi-asserted-by":"publisher","first-page":"7292","DOI":"10.1128\/AAC.03666-14","volume":"58","author":"A Ruecker","year":"2014","unstructured":"Ruecker, A. et al. A male and female gametocyte functional viability assay to identify biologically relevant malaria transmission-blocking drugs. Antimicrob. Agents Chemother. 58, 7292\u20137302 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"BFnrd4683_CR80","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/0470846526.ch8","volume":"217","author":"I Orme","year":"1998","unstructured":"Orme, I. Cellular and genetic mechanisms underlying susceptibility of animal models to tuberculosis infection. Novartis Found. Symp. 217, 112\u2013117; discussion 117\u2013119 (1998).","journal-title":"Novartis Found. Symp."},{"key":"BFnrd4683_CR81","doi-asserted-by":"publisher","first-page":"87","DOI":"10.4161\/chan.2.2.6004","volume":"2","author":"BT Priest","year":"2008","unstructured":"Priest, B. T., Bell, I. M. & Garcia, M. L. Role of hERG potassium channel assays in drug development. Channels (Austin) 2, 87\u201393 (2008).","journal-title":"Channels (Austin)"},{"key":"BFnrd4683_CR82","unstructured":"Riss, T. L. et al. Cell viability assays. Assay Guidance Manual [online] , (2004)."}],"container-title":["Nature Reviews Drug Discovery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nrd4683.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrd4683","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrd4683.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:26:30Z","timestamp":1684452390000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrd4683"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,5]]},"references-count":82,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["BFnrd4683"],"URL":"https:\/\/doi.org\/10.1038\/nrd4683","relation":{},"ISSN":["1474-1776","1474-1784"],"issn-type":[{"value":"1474-1776","type":"print"},{"value":"1474-1784","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,5]]},"assertion":[{"value":"5 October 2015","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}