{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:39:44Z","timestamp":1790667584961,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001559","name":"Breast Cancer Foundation New Zealand","doi-asserted-by":"publisher","award":["1111"],"award-info":[{"award-number":["1111"]}],"id":[{"id":"10.13039\/501100001559","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001552","name":"Cancer Research Trust New Zealand","doi-asserted-by":"publisher","award":["GOT 1717 JGPDF"],"award-info":[{"award-number":["GOT 1717 JGPDF"]}],"id":[{"id":"10.13039\/501100001552","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine patients\u2019 immune systems, leading to poor disease outcomes. Both enzymes are validated targets for cancer immunotherapy but there is a paucity of potent TDO2 and dual IDO1\/TDO2 inhibitors. To identify novel dual IDO1\/TDO2 scaffolds, 3D shape similarity and pharmacophore in silico screening was conducted using TDO2 as a model for both systems. The obtained hits were tested in cancer cell lines expressing mainly IDO1 (SKOV3\u2014ovarian), predominantly TDO2 (A172\u2014brain), and both IDO1 and TDO2 (BT549\u2014breast). Three virtual screening hits were confirmed as inhibitors (TD12, TD18 and TD34). Dose response experiments showed that TD34 is the most potent inhibitor capable of blocking both IDO1 and TDO2 activity, with the IC50 value for BT549 at 3.42 \u00b5M. This work identified new scaffolds able to inhibit both IDO1 and TDO2, thus enriching the collection of dual IDO1\/TDO2 inhibitors and providing chemical matter for potential development into future anticancer drugs.<\/jats:p>","DOI":"10.3390\/molecules24234346","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T08:14:04Z","timestamp":1574928844000},"page":"4346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Discovery and Characterisation of Dual Inhibitors of Tryptophan 2,3-Dioxygenase (TDO2) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Using Virtual Screening"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8248-4218","authenticated-orcid":false,"given":"Suat","family":"Sari","sequence":"first","affiliation":[{"name":"Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5490-6540","authenticated-orcid":false,"given":"Petr","family":"Tomek","sequence":"additional","affiliation":[{"name":"Auckland Cancer Society Research Centre, University of Auckland, Grafton, 1023 Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euphemia","family":"Leung","sequence":"additional","affiliation":[{"name":"Auckland Cancer Society Research Centre, University of Auckland, Grafton, 1023 Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-9512","authenticated-orcid":false,"given":"J\u00f3hannes","family":"Reynisson","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Bioengineering, Keele University, Hornbeam building, Staffordshire ST5 5BG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41573-019-0016-5","article-title":"Tryptophan Metabolism as a Common Therapeutic Target in Cancer, Neurodegeneration and Beyond. 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