{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:46:08Z","timestamp":1790667968448,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["190096"],"award-info":[{"award-number":["190096"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["708048"],"award-info":[{"award-number":["708048"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:p>Brain metastases (BM) occur in 26% of cancer patients and have a 90% mortality rate within 1 y of diagnosis, yet the current standard of care remains palliative. We have previously shown that de novo GTP synthesis is a druggable metabolic vulnerability in BM cells, through its rate-limiting enzyme, inosine monophosphate dehydrogenase (IMPDH). IMPDH inhibitors have progressed to phase-II oncology trials in the past, failing largely due to dose-limiting toxicities associated with off-target inhibition of IMPDH1, the constitutively expressed isoenzyme in normal human lymphocytes. Here, we determined that a single subtype (isoenzyme) of IMPDH, IMPDH2, is specifically upregulated in brain metastasis-initiating cells (BMICs), absent in normal brain tissue, and is sufficient to drive the formation of BM. Moreover, we show that genetic knockout of IMPDH2 stops the proliferation of BM cells in vitro and the onset of BM in vivo. We synthesized IMPDH2-selective compounds and showed that they maintain a potent antiproliferation effect on BMICs, but spare immune cell function compared to previously developed pan-IMPDH inhibitors. Furthermore, we introduce a positive correlation between compound selectivity for IMPDH2 and the ability to synergize with Osimertinib: the standard of care for EGFR-mutant non\u2013small cell lung cancer. Overall, our results suggest that specifically blocking IMPDH2 is an effective therapeutic strategy for BM by overcoming the immune suppressive effects that have hindered the clinical development of pan-IMPDH inhibitors in the past. An IMPDH2 specific therapy could be coadministered with primary tumor standard of care treatments to provide a safe and interceptional approach for BM.<\/jats:p>","DOI":"10.1073\/pnas.2603440123","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:08:59Z","timestamp":1781712539000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Selectively targeting inosine monophosphate dehydrogenase-2 impairs brain metastatic potential while preserving immune cell function"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5176-4890","authenticated-orcid":false,"given":"Agata M.","family":"Kieliszek","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]},{"name":"Block Biosciences","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6491-1696","authenticated-orcid":false,"given":"Erika","family":"Apel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suky","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew","family":"Piotrowski","sequence":"additional","affiliation":[{"name":"Block Biosciences","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Chui","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Alazet","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeideh","family":"Shamsi","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mobilio","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarrod W.","family":"Johnson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7385-673X","authenticated-orcid":false,"given":"Laura","family":"Escudero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Vandevoorde","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Mei","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Vancouver, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Acevedo","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Sabbatani","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6494-4383","authenticated-orcid":false,"given":"Oliver A.","family":"Kent","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Dordahan","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Yadav","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"MacKay","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-4157","authenticated-orcid":false,"given":"Kevin","family":"Leguay","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J.","family":"Berger","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Miletic","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Zhai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Huebner","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04tnbqb63","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute","place":["London, England, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Oncology, Cancer Research United Kingdom Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London","place":["London, England, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8802-651X","authenticated-orcid":false,"given":"Shawn C.","family":"Chafe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sturino","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janek","family":"Szychowski","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra","family":"Venugopal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Mancini","sequence":"additional","affiliation":[{"name":"adMare BioInnovations","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amie L.","family":"Phinney","sequence":"additional","affiliation":[{"name":"Block Biosciences","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2947-8580","authenticated-orcid":false,"given":"Jakob","family":"Magolan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"name":"Block Biosciences","place":["Hamilton, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1272-5300","authenticated-orcid":false,"given":"Sheila K.","family":"Singh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Discovery and Cancer Research, Faculty of Health Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Surgery, McMaster University","place":["Hamilton, Canada"]},{"name":"Block Biosciences","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/02fa3aq29","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, Canada"]},{"id":[{"id":"https:\/\/ror.org\/0220mzb33","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Comprehensive Cancer Centre, King\u2019s College","place":["London, London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-018-1013-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0305-7372(03)00105-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41016-018-0149-0"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00297-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/20450907.2024.2395804"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt022"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-1022"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4742"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205247120"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101755"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1757-z"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11091346"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)74247-1"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)00026-V"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr900021w"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.12082"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0363-9"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0980-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0207"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3288"},{"key":"e_1_3_4_21_2","first-page":"89","article-title":"The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice","volume":"27","author":"Decker C. J.","year":"2001","unstructured":"C. J. Decker , The novel IMPDH inhibitor VX-497 prolongs skin graft survival and improves graft versus host disease in mice. Drugs Exp. Clin. Res. 27, 89\u201395 (2001).","journal-title":"Drugs Exp. Clin. Res."},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2004.11.015"},{"key":"e_1_3_4_23_2","unstructured":"M. J. Broadhurst \u201cOxamides as Inosine Monophosphate Dehydrogenase (IMPDH) Inhibitors\u201d. EP1127883A2 (2001)."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","unstructured":"T. G. Murali Dhar Discovery of N-[2-[2-[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity. J. Med. Chem. 45 2127\u20132130 (2002).","DOI":"10.1021\/jm0105777"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00944-7"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb17144.x"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-0390-0_5"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","unstructured":"M. Seyfrid In vitro self-renewal assays for brain tumor stem cells (Springer Nature Link 2019) 10.1007\/978-1-4939-8805-1_7.","DOI":"10.1007\/978-1-4939-8805-1_7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","unstructured":"M. Singh N. Savage S. K. Singh In vivo murine models of brain metastasis (Springer Nature Link 2019) 10.1007\/978-1-4939-8805-1_19.","DOI":"10.1007\/978-1-4939-8805-1_19"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23788"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9607416"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00456a001"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-011-0203-y"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adu2459"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2027071"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34889-z"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2020.1834902"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17512-x"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0437"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00220"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205247120"},{"key":"e_1_3_4_42_2","volume-title":"Brain Tumor Stem Cells: Methods and Protocols","author":"Singh S.","unstructured":"S. Singh, C. Venugopal, Brain Tumor Stem Cells: Methods and Protocols (Springer Nature Link, 2019)."},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15885-6"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05706-4"},{"key":"e_1_3_4_46_2","unstructured":"A. M. Kieliszek Metabolomics raw data and table of extracted peak areas for BT478 BT530 and NHA cells cultured in the presence of MPA Compound 3 (IC80) or vehicle control for 6 hours. Figshare. https:\/\/doi.org\/10.6084\/m9.figshare.22246258.v1. Deposited 3 June 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2603440123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:09:55Z","timestamp":1781712595000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2603440123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":46,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2026,6,23]]}},"alternative-id":["10.1073\/pnas.2603440123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2603440123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"assertion":[{"value":"2026-02-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2603440123"}}