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We present a fully automated image\u2010based centrosome\u2010duplication assay that is accurate and robust enough for both careful cell\u2010biology studies and high\u2010throughput screening, and employ this assay in a series of chemical\u2010genetic studies. We observe that a simple cytometric profiling strategy, which is based on organelle size, groups compounds with similar mechanisms of action; this suggests a simple strategy for excluding compounds that undesirably target such activities as protein synthesis and microtubule dynamics. Screening a library of compounds of known activity, we found unexpected effects on centrosome duplication by a number of drugs, most notably isoform\u2010specific protein kinase C inhibitors and retinoic acid receptor agonists. From a 16\u2009320\u2010member library of uncharacterized small molecules, we identified five potent centrosome\u2010duplication inhibitors that do not target microtubule dynamics or protein synthesis. The analysis methodology reported here is directly relevant to studies of centrosome regulation in a variety of systems and is adaptable to a wide range of other biological problems.<\/jats:italic><\/jats:p>","DOI":"10.1002\/cbic.200400266","type":"journal-article","created":{"date-parts":[[2004,11,29]],"date-time":"2004-11-29T04:16:55Z","timestamp":1101701815000},"page":"145-151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["High\u2010Content Screening and Profiling of Drug Activity in an Automated Centrosome\u2010Duplication Assay"],"prefix":"10.1002","volume":"6","author":[{"given":"Zachary E.","family":"Perlman","sequence":"first","affiliation":[]},{"given":"Timothy J.","family":"Mitchison","sequence":"additional","affiliation":[]},{"given":"Thomas U.","family":"Mayer","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,1,7]]},"reference":[{"key":"e_1_2_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02085-2"},{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205772"},{"key":"e_1_2_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00654-8"},{"key":"e_1_2_4_4_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukaryotGeneExpr.v13.i1.20"},{"key":"e_1_2_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc924"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2003.11.006"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.1.105"},{"key":"e_1_2_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0169(1999)42:1<60::AID-CM6>3.0.CO;2-7"},{"key":"e_1_2_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(01)67018-3"},{"key":"e_1_2_4_10_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205102"},{"key":"e_1_2_4_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/138620703106298527"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1201\/9781420040760"},{"key":"e_1_2_4_13_2","unstructured":"Q. 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