{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:05:47Z","timestamp":1780625147181,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,10]],"date-time":"2013-01-10T00:00:00Z","timestamp":1357776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:p>African trypanosomiasis is a neglected tropical disease affecting humans and animals across 36 sub\u2010Saharan African countries. We have investigated the potential to exploit a \u2018piggyback\u2019 approach to inhibit <jats:italic>Trypanosoma brucei<\/jats:italic> transmission by targeting the key developmental regulator of transmission, <jats:italic>T.\u00a0brucei<\/jats:italic> protein tyrosine phosphatase 1. This strategy took advantage of the extensive investment in inhibitors for human protein tyrosine phosphatase 1B, a key target for pharmaceutical companies for the treatment of obesity and diabetes. Structural predictions for human and trypanosome tyrosine phosphatases revealed the overall conservation of important functional motifs, validating the potential for exploiting cross specific compounds. Thereafter, nineteen inhibitors were evaluated; seventeen from a protein tyrosine phosphatase 1B\u2010targeted inhibitor library and two from literature analysis \u2013 oleanolic acid and suramin, the latter of which is a front line drug against African trypanosomiasis. The compounds tested displayed similar inhibitory activities against the human and trypanosome enzymes, mostly behaving as noncompetitive inhibitors. However, their activity against <jats:italic>T.\u00a0brucei<\/jats:italic> in culture was low, necessitating further chemical modification to improve their efficacy and specificity. Nonetheless, the results validate the potential to explore a \u2018piggyback\u2019 strategy targeting <jats:italic>T.\u00a0brucei<\/jats:italic> protein tyrosine phosphatase 1 through exploiting the large pharmacological investment in therapies for obesity targeting protein tyrosine phosphatase 1B.<\/jats:p>","DOI":"10.1111\/cbdd.12079","type":"journal-article","created":{"date-parts":[[2012,10,15]],"date-time":"2012-10-15T17:37:30Z","timestamp":1350322650000},"page":"291-301","source":"Crossref","is-referenced-by-count":5,"title":["Investigating Mammalian Tyrosine Phosphatase Inhibitors as Potential \u2018Piggyback\u2019 Leads to Target <i>Trypanosoma brucei<\/i> Transmission"],"prefix":"10.1111","volume":"81","author":[{"given":"Irene","family":"Ruberto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"Szoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,10]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1544"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01681"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801599"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200605090"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0248-4900(88)90070-6"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(86)90033-0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.323404"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.570310"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(00)01839-0"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1079\/BER2003234"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2001.00803.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1984.11811824"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/2181273a0"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)01043-2"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07997"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212491200"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7540771"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti770"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.108860"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.21.7117-7136.2001"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00137-4"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.13420"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2010.06.003"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312488200"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.07.053"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(77)90040-6"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.07.080"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(95)90032-2"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(87)90461-X"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10771"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60829-1"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182009006416"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(05)61005-6"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2684"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb803"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.2.843"}],"container-title":["Chemical Biology &amp; 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