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Proceeding with the assumption that the active TDH enzyme should be essential for the growth and viability of mouse ES cells, we performed a drug screen in search of specific inhibitors of the purified TDH enzyme. Such efforts led to the discovery of a class of quinazolinecarboxamide (Qc) compounds that inhibit the ability of the TDH enzyme to catabolize threonine into glycine and acetyl-CoA. Administration of Qc inhibitors of TDH to mouse ES cells impeded cell growth and resulted in the induction of autophagy. By contrast, the same chemicals failed to affect the growth of HeLa cells at concentrations 300-fold higher than that required to kill mouse ES cells. It was likewise observed that the Qc class of TDH inhibitors failed to affect the growth or viability of ES cell-derived embryoid body cells known to have extinguished TDH expression. These studies demonstrate how it is possible to kill a specific mammalian cell type on the basis of its specialized metabolic state.<\/jats:p>","DOI":"10.1073\/pnas.1111312108","type":"journal-article","created":{"date-parts":[[2011,9,6]],"date-time":"2011-09-06T22:38:14Z","timestamp":1315348694000},"page":"15828-15833","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Targeted killing of a mammalian cell based upon its specialized metabolic state"],"prefix":"10.1073","volume":"108","author":[{"given":"Peter B.","family":"Alexander","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Cancer Biology, Duke University Medical School, Durham, NC 27710; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9152"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven L.","family":"McKnight","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9152"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,9,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.87.2259.350.b"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86714-5"},{"key":"e_1_3_3_3_2","first-page":"22","article-title":"Metronidazole versus anaerobes. 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