{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:04:15Z","timestamp":1789693455560,"version":"4.0.1"},"posted":{"date-parts":[[2025,8,27]]},"group-title":"Cancer Biology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["R35-CA210068"],"award-info":[{"award-number":["R35-CA210068"]}]},{"name":"National Cancer Institute","award":["K00-CA253731"],"award-info":[{"award-number":["K00-CA253731"]}]},{"name":"National Cancer Institute","award":["K08-CA252611"],"award-info":[{"award-number":["K08-CA252611"]}]},{"name":"National Cancer Institute","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}]},{"name":"National Cancer Institute","award":["ZIA BC 011854"],"award-info":[{"award-number":["ZIA BC 011854"]}]},{"name":"National Cancer Institute","award":["R01-CA276350"],"award-info":[{"award-number":["R01-CA276350"]}]},{"award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"https:\/\/ror.org\/0348ff195","id-type":"ROR","asserted-by":"publisher"}]},{"award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Extramural and the Intramural Research Programs of the NIH","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Many genetically validated targets in cancer, including the transcription factor \u03b2-catenin (\u03b2-cat), have historically been viewed as undruggable. Cell-based phenotypic screening of chemical compounds can reveal new biological and pharmacological principles. Natural products are powerful probes because of their superior structural diversity, drug-like properties, and biological activities as compared to unoptimized synthetic compounds. We screened 326,304 natural product mixtures (40,744 extracts and 285,560 fractions derived from them) using mammalian cells expressing an oncogenic version of \u03b2-cat fused to a suicide protein. Multiple fractions degraded the \u03b2-cat fusion protein or drove it into a compartment where both fusion partners were apparently inactive. The active natural product from one of the latter specifically activates novel, but not classical, protein kinase Cs (PKCs) and thereby relocates \u03b2-cat to juxtamembrane vacuolar structures. These findings suggest a path for inactivating oncogenic \u03b2-cat and underscore the power of screening natural product collections with robust phenotypic assays.<\/jats:p>","DOI":"10.1101\/2025.08.27.671140","type":"posted-content","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T02:50:16Z","timestamp":1756349416000},"source":"Crossref","is-referenced-by-count":1,"title":["Positive Selection Screen Identifies Natural Product \u03b2-Catenin Inactivators"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-1167","authenticated-orcid":false,"given":"Matthew W.","family":"Boudreau","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor F.","family":"Freire","sequence":"additional","affiliation":[{"name":"Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie C.","family":"Corbett","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucero","family":"Mart\u00ednez-Fructuoso","sequence":"additional","affiliation":[{"name":"Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa R.","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohitesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Natural Products Support Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Thornburg","sequence":"additional","affiliation":[{"name":"Natural Products Support Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhone K.","family":"Akee","sequence":"additional","affiliation":[{"name":"Natural Products Support Group, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Peyser","sequence":"additional","affiliation":[{"name":"Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Splaine","sequence":"additional","affiliation":[{"name":"ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Pfaff","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin C.","family":"Chandler","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinah M.","family":"Abeja","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"Lampson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo G.","family":"Kazanietz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Szajner","sequence":"additional","affiliation":[{"name":"ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Smith","sequence":"additional","affiliation":[{"name":"ICCB-Longwood Screening Facility, Harvard Medical School, Boston, MA"},{"name":"Department of Immunology, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidyasagar","family":"Koduri","sequence":"additional","affiliation":[{"name":"Division of Hematology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Grkovic","sequence":"additional","affiliation":[{"name":"Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD"},{"name":"Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"O\u2019Keefe","sequence":"additional","affiliation":[{"name":"Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, MD"},{"name":"Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0574-4856","authenticated-orcid":false,"suffix":"Jr.","given":"William G.","family":"Kaelin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091717201198000_2025.08.27.671140v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.36"},{"key":"2026091717201198000_2025.08.27.671140v2.2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41392-023-01589-z","article-title":"Recent advances in targeting the \u201cundruggable\u201d proteins: from drug discovery to clinical trials","volume":"8","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2026091717201198000_2025.08.27.671140v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0068-6"},{"key":"2026091717201198000_2025.08.27.671140v2.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.ads0239"},{"key":"2026091717201198000_2025.08.27.671140v2.5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccell.2026.01.001","article-title":"Emerging landscape of KRAS inhibitors in cancer treatment","volume":"44","year":"2026","journal-title":"Cancer Cell"},{"key":"2026091717201198000_2025.08.27.671140v2.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244917"},{"key":"2026091717201198000_2025.08.27.671140v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244851"},{"key":"2026091717201198000_2025.08.27.671140v2.8","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.chembiol.2023.06.020","article-title":"The rise of degrader drugs","volume":"30","year":"2023","journal-title":"Cell Chem Biol"},{"key":"2026091717201198000_2025.08.27.671140v2.9","doi-asserted-by":"crossref","unstructured":"V. Koduri et al., Targeting oncoproteins with a positive selection assay for protein degraders. Sci Adv 7, (2021).","DOI":"10.1126\/sciadv.abd6263"},{"key":"2026091717201198000_2025.08.27.671140v2.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.06.012"},{"key":"2026091717201198000_2025.08.27.671140v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.32"},{"key":"2026091717201198000_2025.08.27.671140v2.12","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-0190"},{"key":"2026091717201198000_2025.08.27.671140v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2018.06.003"},{"key":"2026091717201198000_2025.08.27.671140v2.14","doi-asserted-by":"crossref","first-page":"TPS3175","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS3175","article-title":"A first-in-human, phase 1\/2 trial of FOG-001, a \u03b2-catenin:TCF antagonist, in patients with locally advanced or metastatic solid tumors","volume":"42","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026091717201198000_2025.08.27.671140v2.15","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00228"},{"key":"2026091717201198000_2025.08.27.671140v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.022"},{"key":"2026091717201198000_2025.08.27.671140v2.17","doi-asserted-by":"publisher","DOI":"10.1021\/jm501603h"},{"key":"2026091717201198000_2025.08.27.671140v2.18","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/s43018-023-00609-9","article-title":"WNTinib is a multi-kinase inhibitor with specificity against beta-catenin mutant hepatocellular carcinoma","volume":"4","year":"2023","journal-title":"Nat Cancer"},{"key":"2026091717201198000_2025.08.27.671140v2.19","unstructured":"DepMap., DepMap Public 25Q2. Broad, depmap.org (2025)."},{"key":"2026091717201198000_2025.08.27.671140v2.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00763-x"},{"key":"2026091717201198000_2025.08.27.671140v2.21","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1039\/C9NP00068B","article-title":"Creating and screening natural product libraries","volume":"37","year":"2020","journal-title":"Nat Prod Rep"},{"key":"2026091717201198000_2025.08.27.671140v2.22","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.8b00389"},{"key":"2026091717201198000_2025.08.27.671140v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"2026091717201198000_2025.08.27.671140v2.24","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00139"},{"key":"2026091717201198000_2025.08.27.671140v2.25","doi-asserted-by":"crossref","first-page":"12202","DOI":"10.1039\/C4RA15966G","article-title":"Enantiomeric neolignans and sesquineolignans from Jatropha integerrima and their absolute configurations","volume":"5","year":"2015","journal-title":"RSC Adv"},{"key":"2026091717201198000_2025.08.27.671140v2.26","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90611-8"},{"key":"2026091717201198000_2025.08.27.671140v2.27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/26.2.486"},{"key":"2026091717201198000_2025.08.27.671140v2.28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.4.775"},{"key":"2026091717201198000_2025.08.27.671140v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(03)00140-8"},{"key":"2026091717201198000_2025.08.27.671140v2.30","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.5.1087"},{"key":"2026091717201198000_2025.08.27.671140v2.31","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00416-10"},{"key":"2026091717201198000_2025.08.27.671140v2.32","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1039\/C4NP00008K","article-title":"Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators","volume":"31","year":"2014","journal-title":"Nat Prod Rep"},{"key":"2026091717201198000_2025.08.27.671140v2.33","doi-asserted-by":"crossref","unstructured":"F. Vela , A. Ezzanad , A. C. Hunter , A. J. Mac\u00edas-S\u00e1nchez , R. Hern\u00e1ndez-Gal\u00e1n , Pharmacological Potential of Lathyrane-Type Diterpenoids from Phytochemical Sources. Pharmaceuticals (Basel) 15, (2022).","DOI":"10.3390\/ph15070780"},{"key":"2026091717201198000_2025.08.27.671140v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2453-9"},{"key":"2026091717201198000_2025.08.27.671140v2.35","doi-asserted-by":"crossref","first-page":"14898","DOI":"10.1016\/S0021-9258(18)82418-8","article-title":"Mechanism of lipopolysaccharide-triggered junB activation in a mouse macrophage-like cell line (J774)","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"2026091717201198000_2025.08.27.671140v2.36","doi-asserted-by":"crossref","unstructured":"S. Dupasquier et al., Modulating PKC\u03b1 Activity to Target Wnt\/\u03b2-Catenin Signaling in Colon Cancer. Cancers (Basel) 11, (2019).","DOI":"10.3390\/cancers11050693"},{"key":"2026091717201198000_2025.08.27.671140v2.37","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.775700"},{"key":"2026091717201198000_2025.08.27.671140v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7156"},{"key":"2026091717201198000_2025.08.27.671140v2.39","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1267"},{"key":"2026091717201198000_2025.08.27.671140v2.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.06.035"},{"key":"2026091717201198000_2025.08.27.671140v2.41","doi-asserted-by":"publisher","DOI":"10.1021\/jm500417b"},{"key":"2026091717201198000_2025.08.27.671140v2.42","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.524"},{"key":"2026091717201198000_2025.08.27.671140v2.43","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.tips.2017.02.002","article-title":"Reversing the Paradigm: Protein Kinase C as a Tumor Suppressor","volume":"38","year":"2017","journal-title":"Trends Pharmacol Sci"},{"key":"2026091717201198000_2025.08.27.671140v2.44","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001068"},{"key":"2026091717201198000_2025.08.27.671140v2.45","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00395.2005"},{"key":"2026091717201198000_2025.08.27.671140v2.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102466"},{"key":"2026091717201198000_2025.08.27.671140v2.47","doi-asserted-by":"crossref","first-page":"113722","DOI":"10.1016\/j.celrep.2024.113722","article-title":"TRPM2 enhances ischemic excitotoxicity by associating with PKC\u03b3","volume":"43","year":"2024","journal-title":"Cell Rep"},{"key":"2026091717201198000_2025.08.27.671140v2.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30389-2"},{"key":"2026091717201198000_2025.08.27.671140v2.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.12.013"},{"key":"2026091717201198000_2025.08.27.671140v2.50","doi-asserted-by":"publisher","DOI":"10.2174\/138945008785132376"},{"key":"2026091717201198000_2025.08.27.671140v2.51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000235"},{"key":"2026091717201198000_2025.08.27.671140v2.52","doi-asserted-by":"crossref","first-page":"115449","DOI":"10.1016\/j.ejmech.2023.115449","article-title":"Synthesis and evaluation of DAG-lactone derivatives with HIV-1 latency reversing activity","volume":"256","year":"2023","journal-title":"Eur J Med Chem"},{"key":"2026091717201198000_2025.08.27.671140v2.53","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604642"},{"key":"2026091717201198000_2025.08.27.671140v2.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.12.022"},{"key":"2026091717201198000_2025.08.27.671140v2.55","doi-asserted-by":"publisher","DOI":"10.1021\/ar020124b"},{"key":"2026091717201198000_2025.08.27.671140v2.56","doi-asserted-by":"crossref","first-page":"6261","DOI":"10.1021\/acs.jmedchem.8b00661","article-title":"alpha-Arylidene Diacylglycerol-Lactones (DAG-Lactones) as Selective Ras Guanine-Releasing Protein 3 (RasGRP3) Ligands","volume":"61","year":"2018","journal-title":"J Med Chem"},{"key":"2026091717201198000_2025.08.27.671140v2.57","doi-asserted-by":"crossref","first-page":"6041","DOI":"10.1038\/s41598-019-42581-4","article-title":"Differential Regulation of Gene Expression in Lung Cancer Cells by Diacyglycerol-Lactones and a Phorbol Ester Via Selective Activation of Protein Kinase C Isozymes","volume":"9","year":"2019","journal-title":"Sci Rep"},{"key":"2026091717201198000_2025.08.27.671140v2.58","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1021\/acs.biochem.3c00375","article-title":"Activation of Munc13-1 by Diacylglycerol (DAG)-Lactones","volume":"62","year":"2023","journal-title":"Biochemistry"},{"key":"2026091717201198000_2025.08.27.671140v2.59","doi-asserted-by":"crossref","first-page":"11418","DOI":"10.1021\/acs.jmedchem.1c00739","article-title":"Design, Synthesis, and Characterization of Novel sn-1 Heterocyclic DAG-Lactones as PKC Activators","volume":"64","year":"2021","journal-title":"J Med Chem"},{"key":"2026091717201198000_2025.08.27.671140v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00865-9"},{"key":"2026091717201198000_2025.08.27.671140v2.61","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168243"},{"key":"2026091717201198000_2025.08.27.671140v2.62","doi-asserted-by":"crossref","first-page":"13147","DOI":"10.1021\/acs.jmedchem.4c01095","article-title":"Genomic Discovery and Structure-Activity Exploration of a Novel Family of Enzyme-Activated Covalent Cyclin-Dependent Kinase Inhibitors","volume":"67","year":"2024","journal-title":"J Med Chem"},{"key":"2026091717201198000_2025.08.27.671140v2.63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008489"},{"key":"2026091717201198000_2025.08.27.671140v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3314"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.08.27.671140","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:20:23Z","timestamp":1789690823000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.08.27.671140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":64,"URL":"https:\/\/doi.org\/10.1101\/2025.08.27.671140","relation":{},"subject":[],"published":{"date-parts":[[2025,8,27]]},"subtype":"preprint"}}