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Although GGCT is a promising target for anti\u2010cancer strategies, no drugs have progressed to clinical availability yet. We established a novel target\u2010based and cell\u2010based screening method for GGCT inhibitors, enabling the efficient discovery of compounds that inhibit intracellular GGCT activity. Using the chemiluminogenic probe LISA\u2010103 in response to GGCT enzymatic activity, high\u2010throughput screening for GGCT inhibitors was performed in lung cancer SW1573 cells. The hit compound plumbagin was identified as a novel GGCT inhibitor that suppressed its activity intracellularly. Plumbagin directly bound to a GGCT\u2010recombinant protein and inhibited its activity. Moreover, plumbagin up\u2010regulated p21, a cyclin\u2010dependent kinase inhibitor, and activated the tumor suppressor RB protein, inhibiting cell growth and cell cycle progression in breast MCF7 and colon HCT116 cancer cell lines. These phenomena induced by plumbagin mimicked the effect of GGCT depletion. The treatment with plumbagin suppressed tumor growth of HCT116 xenograft mice. These results suggest the potential of plumbagin in cancer therapy as a GGCT inhibitor.<\/jats:p>","DOI":"10.1111\/cas.70390","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T09:52:48Z","timestamp":1776073968000},"page":"1713-1723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of a Novel \u03b3\u2010Glutamylcyclotransferase Inhibitor Plumbagin by Luminescence\u2010Based High\u2010Throughput Screening"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-9166","authenticated-orcid":false,"given":"Keiko","family":"Taniguchi","sequence":"first","affiliation":[{"name":"Department of Drug Discovery Medicine Kyoto Prefectural University of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukie","family":"Nohara","sequence":"additional","affiliation":[{"name":"Peptide Institute Inc.  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