{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:01:10Z","timestamp":1789236070181,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2023,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chemical probes are essential tools for understanding biological systems and for credentialing potential biomedical targets. Programmed cell death 2 (PDCD2) is a member of the B\u2010cell lymphoma 2 (Bcl\u20102) family of proteins, which are critical regulators of apoptosis. Here we report the discovery and characterization of <jats:bold>10\u2009e<\/jats:bold>, a first\u2010in\u2010class small molecule degrader of PDCD2. We discovered this PDCD2 degrader by serendipity using a chemical proteomics approach, in contrast to the conventional approach for making bivalent degraders starting from a known binding ligand targeting the protein of interest. Using <jats:bold>10\u2009e<\/jats:bold> as a pharmacological probe, we demonstrate that PDCD2 functions as a critical regulator of cell growth by modulating the progression of the cell cycle in T lymphoblasts. Our work provides a useful pharmacological probe for investigating PDCD2 function and highlights the use of chemical proteomics to discover selective small molecule degraders of unanticipated targets.<\/jats:p>","DOI":"10.1002\/anie.202308292","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T23:03:16Z","timestamp":1693609396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteomics\u2010Based Discovery of First\u2010in\u2010Class Chemical Probes for Programmed Cell Death Protein 2 (PDCD2)"],"prefix":"10.1002","volume":"62","author":[{"given":"Wenzhi","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-3698","authenticated-orcid":false,"given":"Woong Sub","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"},{"name":"Lingang Laboratory  Shanghai 20031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xijun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Dana-Farber Cancer Institute  Boston MA 02215 USA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School  Boston MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan G.","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Dana-Farber Cancer Institute  Boston MA 02215 USA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School  Boston MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmixinuer","family":"Abulaiti","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Corsello","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric S.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology Dana-Farber Cancer Institute  Boston MA 02215 USA"},{"name":"Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School  Boston MA 02115 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5354-7403","authenticated-orcid":false,"given":"Nathanael S.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology Chem-H and Stanford Cancer Institute Stanford School of Medicine Stanford University  Stanford CA 94305 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"e_1_2_3_1_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MD00228G"},{"key":"e_1_2_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.023"},{"key":"e_1_2_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.11.004"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2MD00291D"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4366"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijch.201800113"},{"key":"e_1_2_3_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00193D"},{"key":"e_1_2_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00371-6"},{"key":"e_1_2_3_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01382"},{"key":"e_1_2_3_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-020-00099-9"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042702599"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.11.8.4177"},{"key":"e_1_2_3_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701770104"},{"key":"e_1_2_3_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2010.04.007"},{"key":"e_1_2_3_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205647"},{"key":"e_1_2_3_16_1","first-page":"10894","volume":"8","author":"Yang Y.","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V124.21.1331.1331"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1108"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20148326"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00666-y"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.12.055"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.24484"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3551"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.02.001"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00409-3"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472555220985776"},{"key":"e_1_2_3_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.07.002"},{"key":"e_1_2_3_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00065"},{"key":"e_1_2_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.038"},{"key":"e_1_2_3_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07884"},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13527"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800324m"},{"key":"e_1_2_3_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.10.005"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.31"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-00971-2"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202202770"},{"key":"e_1_2_3_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c11706"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202308292","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:21:20Z","timestamp":1753370480000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202308292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,15]]},"references-count":37,"journal-issue":{"issue":"43","published-print":{"date-parts":[[2023,10,23]]}},"alternative-id":["10.1002\/anie.202308292"],"URL":"https:\/\/doi.org\/10.1002\/anie.202308292","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,15]]},"assertion":[{"value":"2023-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202308292"}}