{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:57:47Z","timestamp":1791644267871,"version":"4.3.4"},"reference-count":69,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/07600-3"],"award-info":[{"award-number":["2013\/07600-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/25658-9"],"award-info":[{"award-number":["2013\/25658-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465637\/2014-0"],"award-info":[{"award-number":["465637\/2014-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology & Therapeutics"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1016\/j.pharmthera.2017.06.004","type":"journal-article","created":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T15:31:28Z","timestamp":1496417488000},"page":"49-61","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":59,"special_numbering":"C","title":["Targeting cysteine proteases in trypanosomatid disease drug discovery"],"prefix":"10.1016","volume":"180","author":[{"given":"Leonardo G.","family":"Ferreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano D.","family":"Andricopulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.pharmthera.2017.06.004_bb0005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000298","article-title":"RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model","volume":"2","author":"Abdulla","year":"2008","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0010","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/intimm\/dxm149","article-title":"Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB\/c immunized mice","volume":"20","author":"Acosta","year":"2008","journal-title":"International Immunology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0015","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1473-3099(10)70223-1","article-title":"Urbanisation and infectious diseases in a globalised world","volume":"11","author":"Alirol","year":"2011","journal-title":"The Lancet Infectious Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0020","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1093\/cid\/cis886","article-title":"Nifurtimox-eflornithine combination therapy for second-stage gambiense human African trypanosomiasis: M\u00e9decins Sans Fronti\u00e8res experience in the Democratic Republic of the Congo","volume":"56","author":"Alirol","year":"2013","journal-title":"Clinical Infectious Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001870","article-title":"Fexinidazole: A potential new drug candidate for Chagas disease","volume":"6","author":"Bahia","year":"2012","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0030","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0166-6851(03)00139-7","article-title":"Specific cleavage sites on human IgG subclasses by cruzipain, the major cysteine proteinase from Trypanosoma cruzi","volume":"130","author":"Berasain","year":"2003","journal-title":"Molecular and Biochemical Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0035","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Research"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0040","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1056\/NEJMra1410150","article-title":"Chagas' disease","volume":"373","author":"Bern","year":"2015","journal-title":"The New England Journal of Medicine"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0045","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1126\/science.1112642","article-title":"The genome of the African trypanosome Trypanosoma brucei","volume":"309","author":"Berriman","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0050","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.2174\/0929867322666150521091652","article-title":"Cruzipain: An update on its potential as chemotherapy target against the human pathogen Trypanosoma cruzi","volume":"22","author":"Branquinha","year":"2015","journal-title":"Current Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0055","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0166-6851(01)00368-1","article-title":"Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense","volume":"118","author":"Caffrey","year":"2001","journal-title":"Molecular and Biochemical Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0060","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1191\/0960327106het653oa","article-title":"Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)","volume":"25","author":"Castro","year":"2006","journal-title":"Human & Experimental Toxicology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0065","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.clinthera.2014.05.004","article-title":"Measuring progress in neglected disease drug development","volume":"36","author":"Cohen","year":"2014","journal-title":"Clinical Therapeutics"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0070","series-title":"Comprehensive analysis of parasite biology: From metabolism to drug discovery: From metabolism to drug discovery","first-page":"121","article-title":"Trypanosomal cysteine peptidases: Target validation and drug design strategies","author":"da Silva","year":"2016"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0075","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1017\/S003118201300142X","article-title":"Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections","volume":"141","author":"Don","year":"2014","journal-title":"Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0080","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1128\/AAC.00436-07","article-title":"A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection","volume":"51","author":"Doyle","year":"2007","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0085","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002139","article-title":"The Trypanosoma cruzi protease cruzain mediates immune evasion","volume":"7","author":"Doyle","year":"2011","journal-title":"PLoS Pathogens"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0090","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1645\/0022-3395(2001)087[1016:EAPEAG]2.0.CO;2","article-title":"Enzymatic activity, protein expression, and gene sequence of cruzipain in virulent and attenuated Trypanosoma cruzi strains","volume":"87","author":"Duschak","year":"2001","journal-title":"The Journal of Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0095","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/cmdc.201300112","article-title":"Optimization of triazine nitriles as rhodesain inhibitors: Structure-activity relationships, bioisosteric imidazopyridine nitriles, and X-ray crystal structure analysis with human cathepsin L","volume":"8","author":"Ehmke","year":"2013","journal-title":"ChemMedChem"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0105","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1126\/science.1112631","article-title":"The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease","volume":"309","author":"El-Sayed","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0110","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1084\/jem.188.4.725","article-title":"Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection","volume":"188","author":"Engel","year":"1998","journal-title":"The Journal of Experimental Medicine"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0115","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1002\/cmdc.201200274","article-title":"Synthesis and molecular modeling studies on derivatives of a highly potent peptidomimetic vinyl ester as falcipain-2 inhibitor","volume":"7","author":"Ettari","year":"2012","journal-title":"ChemMedChem"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0120","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1016\/j.bmc.2015.09.029","article-title":"Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation","volume":"23","author":"Ettari","year":"2015","journal-title":"Bioorganic & Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0125","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.3109\/14756366.2015.1108972","article-title":"Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors","volume":"31","author":"Ettari","year":"2016","journal-title":"Journal of Enzyme Inhibition and Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0130","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0124832","article-title":"Cruzipain activates latent TGF-\u03b2 from host cells during T. cruzi invasion","volume":"10","author":"Ferr\u00e3o","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0135","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1021\/jm401709b","article-title":"Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as anti-Trypanosoma cruzi agents","volume":"57","author":"Ferreira","year":"2014","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0140","doi-asserted-by":"crossref","first-page":"13384","DOI":"10.3390\/molecules200713384","article-title":"Molecular docking and structure-based drug design strategies","volume":"20","author":"Ferreira","year":"2015","journal-title":"Molecules"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0145","doi-asserted-by":"crossref","first-page":"4891","DOI":"10.1021\/jm100488w","article-title":"Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors","volume":"53","author":"Ferreira","year":"2010","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0150","first-page":"257","article-title":"Epidemiology of human African trypanosomiasis","volume":"6","author":"Franco","year":"2014","journal-title":"Journal of Clinical Epidemiology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0155","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1002\/pro.5560060801","article-title":"Structural determinants of specificity in the cysteine protease cruzain","volume":"6","author":"Gillmor","year":"1997","journal-title":"Protein Science"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0160","doi-asserted-by":"crossref","first-page":"11131","DOI":"10.1021\/cr500546h","article-title":"Introduction: Drug discovery and development for neglected diseases","volume":"114","author":"Goupil","year":"2014","journal-title":"Chemical Reviews"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0165","doi-asserted-by":"crossref","first-page":"3212","DOI":"10.1021\/jm030549j","article-title":"Synthesis and structure\u2013activity relationships of parasiticidal thiosemicarbazone cystein protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi","volume":"47","author":"Greenbaum","year":"2004","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0170","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0166-6851(93)90086-D","article-title":"Peptide-fluromethyl ketones arrest intracellular replication and intercellular transmission of Trypanosoma cruzi","volume":"58","author":"Harth","year":"1993","journal-title":"Molecular and Biochemical Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0175","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001151","article-title":"SCYX-7158, an orally-active benzoxaborole for the treatment of stage 2 human African trypanosomiasis","volume":"5","author":"Jacobs","year":"2011","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0180","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001221","article-title":"Innovative partnerships for drug discovery against neglected diseases","volume":"5","author":"Jakobsen","year":"2011","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0185","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/cbdd.12628","article-title":"Screening and identification of inhibitors of Trypanosoma brucei cathepsin L with antitrypanosomal activity","volume":"87","author":"Jefferson","year":"2016","journal-title":"Chemical Biology & Drug Design"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0190","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1021\/acsmedchemlett.5b00336","article-title":"Synthesis and evaluation of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 against cruzain","volume":"7","author":"Jones","year":"2015","journal-title":"ACS Medicinal Chemistry Letters"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0195","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S1474-4422(12)70296-X","article-title":"Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)","volume":"12","author":"Kennedy","year":"2013","journal-title":"Lancet Neurology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0200","doi-asserted-by":"crossref","first-page":"25697","DOI":"10.1074\/jbc.M109.014340","article-title":"Vinyl sulfones as antiparasitic agents and a structural basis for drug design","volume":"284","author":"Kerr","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0205","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0000701","article-title":"Crystal structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei","volume":"4","author":"Kerr","year":"2010","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0210","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nmeth.1859","article-title":"In vivo protein crystallization opens new routes in structural biology","volume":"9","author":"Koopmann","year":"2012","journal-title":"Nature Methods"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0215","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1515\/BC.2002.077","article-title":"Congopain from Trypanosoma congolense: Drug target and vaccine candidate","volume":"383","author":"Lalmanach","year":"2002","journal-title":"Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0220","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1021\/acsmedchemlett.6b00276","article-title":"Dipeptidyl nitroalkenes as potent reversible inhibitors of cysteine proteases rhodesain and cruzain","volume":"7","author":"Latorre","year":"2016","journal-title":"ACS Medicinal Chemistry Letters"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0225","doi-asserted-by":"crossref","first-page":"48426","DOI":"10.1074\/jbc.M402470200","article-title":"A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei","volume":"279","author":"Mackey","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0230","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001857","article-title":"Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: Role of the CNS inflammatory response","volume":"6","author":"MacLean","year":"2012","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0235","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1021\/jm900908p","article-title":"Structure-guided development of selective TbCatB inhibitors","volume":"52","author":"Mallari","year":"2009","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0240","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1021\/jm070760l","article-title":"Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbCatB","volume":"51","author":"Mallari","year":"2008","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0245","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0005033","article-title":"Estimating the burden of Chagas disease in the United States","volume":"10","author":"Manne-Goehler","year":"2016","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0250","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.drudis.2015.02.004","article-title":"Cruzain inhibitors: Efforts made, current leads and a structural outlook of new hits","volume":"20","author":"Martinez-Mayorga","year":"2015","journal-title":"Drug Discovery Today"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0255","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/S0140-6736(16)30171-4","article-title":"Neglected tropical diseases: Progress towards addressing the chronic pandemic","volume":"389","author":"Molyneux","year":"2017","journal-title":"Lancet"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0260","doi-asserted-by":"crossref","first-page":"814","DOI":"10.4269\/ajtmh.13-0726","article-title":"Neglected parasitic infections in the United States: Chagas disease","volume":"90","author":"Montgomery","year":"2014","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0265","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/jm901069a","article-title":"Identification and optimization of inhibitors of trypanosomal cysteine proteases: Cruzain, rhodesain, and TbCatB","volume":"53","author":"Mott","year":"2010","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0270","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1586\/eri.10.144","article-title":"The urgent need to develop new drugs and tools for the treatment of Chagas disease","volume":"9","author":"Mu\u00f1oz","year":"2011","journal-title":"Expert Review of Anti-Infective Therapy"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0275","doi-asserted-by":"crossref","first-page":"4834","DOI":"10.1016\/j.bmcl.2015.06.066","article-title":"Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease","volume":"25","author":"Neitz","year":"2015","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0280","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1172\/JCI27798.","article-title":"Blood-brain barrier traversal by African trypanosomes requires calcium signaling induced by parasite cysteine protease","volume":"116","author":"Nikolskaia","year":"2006","journal-title":"The Journal of Clinical Investigation"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0290","doi-asserted-by":"crossref","first-page":"28934","DOI":"10.1074\/jbc.M805824200","article-title":"A parasite cysteine protease is key to host protein degradation and iron acquisition","volume":"283","author":"O'Brien","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0295","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(01)00438-8","article-title":"Cysteine proteases of parasitic organisms","volume":"120","author":"Sajid","year":"2002","journal-title":"Molecular and Biochemical Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0300","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/j.1365-2958.2007.05970.x","article-title":"Role of the Trypanosoma brucei natural cysteine peptidase inhibitor ICP in differentiation and virulence","volume":"66","author":"Santos","year":"2007","journal-title":"Molecular Microbiology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0305","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.bbrc.2012.08.015","article-title":"On the size of the active site in proteases. I. Papain. 1967","volume":"425","author":"Schechter","year":"2012","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0310","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nchembio.1199","article-title":"Target identification and mechanism of action in chemical biology and drug discovery","volume":"9","author":"Schenone","year":"2013","journal-title":"Nature Chemical Biology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0315","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bmcl.2016.11.036","article-title":"Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine protease of Trypanosoma brucei","volume":"27","author":"Schirmeister","year":"2017","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0320","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/expr.1998.4381","article-title":"Trypanosoma brucei: Killing of bloodstream forms in vitro and in vivo by the cysteine proteinase inhibitor Zphe-ala-CHN2","volume":"91","author":"Scory","year":"1999","journal-title":"Experimental Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0325","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1017\/S0031182012000169","article-title":"Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis","volume":"139","author":"Simarro","year":"2012","journal-title":"Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0330","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.ijpara.2012.03.009","article-title":"Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target","volume":"42","author":"Steverding","year":"2012","journal-title":"International Journal for Parasitology"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0335","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s40262-014-0136-3","article-title":"Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: First-in-human studies","volume":"53","author":"Tarral","year":"2014","journal-title":"Clinical Pharmacokinetics"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0340","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine cathepsins: From structure, function and regulation to new frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochimica et Biophysica Acta"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0345","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1586\/14787210.7.2.157","article-title":"Side effects of benznidazole as treatment in chronic Chagas disease: Fears and realities","volume":"7","author":"Viotti","year":"2009","journal-title":"Expert Review of Anti-Infective Therapy"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0350","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.2174\/156802611795429185","article-title":"Target validation: Linking target and chemical properties to desired product profile","volume":"11","author":"Wyatt","year":"2011","journal-title":"Current Topics in Medicinal Chemistry"},{"key":"10.1016\/j.pharmthera.2017.06.004_bb0355","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1002\/chem.201103322","article-title":"Design, synthesis and biological evaluation of potent azadipeptide nitrile inhibitors and activity-based probes as promising anti-Trypanosoma brucei agents","volume":"18","author":"Yang","year":"2012","journal-title":"Chemistry"}],"container-title":["Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725817301523?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0163725817301523?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,6,19]],"date-time":"2022-06-19T08:22:20Z","timestamp":1655626940000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0163725817301523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":69,"alternative-id":["S0163725817301523"],"URL":"https:\/\/doi.org\/10.1016\/j.pharmthera.2017.06.004","relation":{},"ISSN":["0163-7258"],"issn-type":[{"value":"0163-7258","type":"print"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting cysteine proteases in trypanosomatid disease drug discovery","name":"articletitle","label":"Article Title"},{"value":"Pharmacology & Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pharmthera.2017.06.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}