{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:48:04Z","timestamp":1792298884761,"version":"4.4.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"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":[[2008,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Development of a safe, effective, and inexpensive therapy for African trypanosomiasis is an urgent priority. In this study, we evaluated the validity of\n            <jats:italic>Trypanosoma brucei<\/jats:italic>\n            glycogen synthase kinase 3 (GSK-3) as a potential drug target. Interference with the RNA of either of two GSK-3 homologues in bloodstream-form\n            <jats:italic>T. brucei<\/jats:italic>\n            parasites led to growth arrest and altered parasite morphology, demonstrating their requirement for cell survival. Since the growth arrest after RNA interference appeared to be more profound for\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 \u201cshort\u201d (Tb10.161.3140) than for\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 \u201clong\u201d (Tb927.7.2420), we focused on\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short for further studies.\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short with an N-terminal maltose-binding protein fusion was cloned, expressed, and purified in a functional form. The potency of a GSK-3-focused inhibitor library against the recombinant enzyme of\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short, as well as bloodstream-form parasites, was evaluated with the aim of determining if compounds that inhibit enzyme activity could also block the parasites' growth and proliferation. Among the compounds active against the cell, there was an excellent correlation between activity inhibiting the\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short enzyme and the inhibition of\n            <jats:italic>T. brucei<\/jats:italic>\n            growth. Thus, there is reasonable genetic and chemical validation of GSK-3 short as a drug target for\n            <jats:italic>T. brucei<\/jats:italic>\n            . Finally, selective inhibition may be required for therapy targeting the GSK-3 enzyme, and a molecular model of the\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short enzyme suggests that compounds that selectively inhibit\n            <jats:italic>T. brucei<\/jats:italic>\n            GSK-3 short over the human GSK-3 enzymes can be found.\n          <\/jats:p>","DOI":"10.1128\/aac.00364-08","type":"journal-article","created":{"date-parts":[[2008,7,22]],"date-time":"2008-07-22T00:45:39Z","timestamp":1216687539000},"page":"3710-3717","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["Glycogen Synthase Kinase 3 Is a Potential Drug Target for African Trypanosomiasis Therapy"],"prefix":"10.1128","volume":"52","author":[{"given":"Kayode K.","family":"Ojo","sequence":"first","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Robert","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Riechers","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J.","family":"Napuli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe L. M. J.","family":"Verlinde","sequence":"additional","affiliation":[{"name":"Department of Biochemistry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick S.","family":"Buckner","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Gelb","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Washington, Seattle, Washington 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias M.","family":"Domostoj","sequence":"additional","affiliation":[{"name":"Merck-Serono Geneva Research Centre, Merck-Serono International S.A. Chemin des Mines 9, Geneva CH-1202, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Wells","sequence":"additional","affiliation":[{"name":"Merck-Serono Geneva Research Centre, Merck-Serono International S.A. Chemin des Mines 9, Geneva CH-1202, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Scheer","sequence":"additional","affiliation":[{"name":"Merck-Serono Geneva Research Centre, Merck-Serono International S.A. Chemin des Mines 9, Geneva CH-1202, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy N. C.","family":"Wells","sequence":"additional","affiliation":[{"name":"Merck-Serono Geneva Research Centre, Merck-Serono International S.A. Chemin des Mines 9, Geneva CH-1202, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley C.","family":"Van Voorhis","sequence":"additional","affiliation":[{"name":"Division of Allergy and Infectious Diseases, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1074\/mcp.T400008-MCP200","volume":"3","year":"2004","unstructured":"Alexandrov, A., M. Vignali, D. J. LaCount, E. Quartley, C. de Vries, D. De Rosa, J. Babulski, S. F. Mitchell, L. W. Schoenfeld, S. Fields, W. G. Hol, M. E. Dumont, E. M. Phizicky, and E. J. Grayhack. 2004. A facile method for high-throughput co-expression of protein pairs. Mol. Cell. Proteomics3:934-938.","journal-title":"Mol. Cell. Proteomics"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.10.002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.06.013"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"7115","DOI":"10.1093\/nar\/17.17.7115","volume":"17","year":"1989","unstructured":"Barbu, V., and F. Dautry. 1989. Northern blot normalization with a 28S rRNA oligonucleotide probe. Nucleic Acids Res.17:7115.","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2082"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00374-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bbapap.2003.11.023","volume":"1697","year":"2004","unstructured":"Droucheau, E., A. Primot, V. Thomas, D. Mattei, M. Knockaert, C. Richardson, P. Sallicandro, P. Alano, A. Jafarshad, B. Baratte, C. Kunick, D. Parzy, L. Pearl, C. Doerig, and L. Meijer. 2004. Plasmodium falciparum glycogen synthase kinase-3: molecular model, expression, intracellular localisation and selective inhibitors. Biochim. Biophys. Acta1697:181-196.","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2007.01.001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2003.09.002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3590001"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.8.3033-3042.2004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300813200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401276200"},{"key":"e_1_3_2_15_2","first-page":"91","volume":"5","year":"2003","unstructured":"Hammarton, T. C., J. C. Mottram, and C. Doerig. 2003. The cell cycle of parasitic protozoa: potential for chemotherapeutic exploitation. Prog. Cell Cycle Res.5:91-101.","journal-title":"Prog. Cell Cycle Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.2307\/3282883"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1471-4159.2004.03004.x","volume":"93","year":"2005","unstructured":"Johnson, K., L. Liu, N. Majdzadeh, C. Chavez, P. C. Chin, B. Morrison, L. Wang, J. Park, P. Chugh, H. M. Chen, and S. R. D'Mello. 2005. Inhibition of neuronal apoptosis by the cyclin-dependent kinase inhibitor GW8510: identification of 3\u2032 substituted indolones as a scaffold for the development of neuroprotective drugs. J. Neurochem.93:538-548.","journal-title":"J. Neurochem."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/cbic.200400099","volume":"6","year":"2005","unstructured":"Kunick, C., Z. Zeng, R. Gussio, D. Zaharevitz, M. Leost, F. Totzke, C. Sch\u00e4chtele, M. H. G. Kubbutat, L. Meijer, and T. Lemcke. 2005. Structure-aided optimization of kinase inhibitors derived from alsterpaullone. Chembiochem6:541-549.","journal-title":"Chembiochem"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1021\/jm0608107","volume":"50","year":"2007","unstructured":"Liao, J. J. 2007. Molecular recognition of protein kinase binding pockets for design of potent and selective kinase inhibitors. J. Med. Chem.50:409-424.","journal-title":"J. Med. Chem."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007907728892"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(93)90231-L"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.03.011"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.07.006"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2005.08.018"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.8.2444"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd1824","volume":"4","year":"2005","unstructured":"Pink, R., A. Hudson, M. A. Mouries, and M. Bendig. 2005. Opportunities and challenges in antiparasitic drug discovery. Nat. Rev. Drug Discov.4:727-740.","journal-title":"Nat. Rev. Drug Discov."},{"key":"e_1_3_2_27_2","first-page":"147","volume":"1114","year":"1992","unstructured":"Plyte, S. E., K. Hughes, E. Nikolakaki, B. J. Pulverer, and J. R. Woodgett. 1992. Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim. Biophys. Acta1114:147-162.","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1021\/jm031016d","volume":"47","year":"2004","unstructured":"Polychronopoulos, P., P. Magiatis, A. L. Skaltsounis, V. Myrianthopoulos, E. Mikros, A. Tarricone, A. Musacchio, S. M. Roe, L. Pearl, M. Leost, P. Greengard, and L. Meijer. 2004. Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J. Med. Chem.47:935-946.","journal-title":"J. Med. Chem."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(97)00079-X"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(03)00045-8"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3030701"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.4.755-764.2005"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36661-9"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00002-X"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00364-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00364-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T19:24:49Z","timestamp":1645471489000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00364-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":33,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,10]]}},"alternative-id":["10.1128\/AAC.00364-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.00364-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10]]},"assertion":[{"value":"2008-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}