{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:32:38Z","timestamp":1781101958054,"version":"3.54.1"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,10]]},"abstract":"<jats:p>Small molecule inhibitors provide powerful tools to characterize highly dynamic and complex eukaryotic cell pathways such as those mediating membrane traffic. However, a lack of easy and generalizable assays has constrained identification of novel inhibitors despite availability of diverse chemical libraries. Here, we report a facile growth-based strategy in yeast to screen for pathway-specific inhibitors. The approach uses well characterized synthetic genetic growth defects to guide design of cells genetically sensitized for inhibition of chosen pathways. With this strategy, we identified a family of piperazinyl phenylethanone compounds as inhibitors of traffic between the trans-Golgi network (TGN) and endosomes that depends on the clathrin adaptor complex AP-1. The compounds did not significantly alter other trafficking pathways involving the TGN or endosomes, indicating specificity. Compound treatment also altered localization of AP-1 in mammalian cells. These previously uncharacterized inhibitors will be useful for future studies of clathrin-mediated transport in yeast, and potentially in other organisms. Furthermore, the easily automated technology should be adaptable for identification of inhibitors of other cellular processes.<\/jats:p>","DOI":"10.1073\/pnas.0607773104","type":"journal-article","created":{"date-parts":[[2007,4,2]],"date-time":"2007-04-02T21:04:22Z","timestamp":1175547862000},"page":"6235-6240","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Composite synthetic lethal identification of membrane traffic inhibitors"],"prefix":"10.1073","volume":"104","author":[{"given":"Mara C.","family":"Duncan","sequence":"first","affiliation":[{"name":"Departments of *Biological Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; 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