{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T13:11:16Z","timestamp":1772457076855,"version":"3.50.1"},"reference-count":53,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,4,15]]},"abstract":"<jats:p>HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5\u00a0\u03bcM (MAL3-101), 3.3\u00a0\u03bcM (equisetin) and 7\u00a0\u03bcM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify \u2018new chemical entities\u2019 (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.<\/jats:p>","DOI":"10.1042\/bj20081787","type":"journal-article","created":{"date-parts":[[2009,2,5]],"date-time":"2009-02-05T15:55:30Z","timestamp":1233849330000},"page":"507-517","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an <i>in vitro<\/i> system for discovery of anti-trypanosomal chemical entities"],"prefix":"10.1042","volume":"419","author":[{"given":"Bhargavi","family":"Patham","sequence":"first","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josh","family":"Duffy","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard\u00a0C.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Wipf","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Pittsburgh, Chevron Science Center, 219 Parkman Avenue, Pittsburgh, PA 15260, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheara\u00a0W.","family":"Fewell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey\u00a0L.","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Pittsburgh, 4249 Fifth Avenue, Pittsburgh, PA 15260, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kojo","family":"Mensa-Wilmot","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2009,3,27]]},"reference":[{"key":"2021112214393518300_B1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nchembio837","article-title":"Drug discovery and development for neglected parasitic diseases","volume":"2","author":"Renslo","year":"2006","journal-title":"Nat. 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