{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:37:48Z","timestamp":1790689068024,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["SBP-4"],"award-info":[{"award-number":["SBP-4"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["SBP-8"],"award-info":[{"award-number":["SBP-8"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["Open Fund - Young Individual Research Grant"],"award-info":[{"award-number":["Open Fund - Young Individual Research Grant"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2021,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Targeted covalent inhibitors have re\u2010emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the structure\u2010based design of BCR\u2010ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild\u2010type and mutant ABL kinases, especially ABL\n                    <jats:sup>T315I<\/jats:sup>\n                    bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on molecular recognition of the non\u2010covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co\u2010crystal structures of covalent inhibitor\u2010ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label\u2010free mass spectrometry to evaluate off\u2010targets of our compounds at proteome\u2010wide level in different mammalian cells.\n                  <\/jats:p>","DOI":"10.1002\/anie.202105383","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T04:26:06Z","timestamp":1621398366000},"page":"17131-17137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Strategic Design of Catalytic Lysine\u2010Targeting Reversible Covalent BCR\u2010ABL Inhibitors**"],"prefix":"10.1002","volume":"60","author":[{"given":"David","family":"Quach","sequence":"first","affiliation":[{"name":"NUS Graduate School for Integrative Sciences and Engineering  21 Lower Kent Ridge, University Hall, Tan China Tuan Wing, #04-02 Singapore 119077 Singapore"},{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Chemistry National University of Singapore  Singapore 117543 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jothi","family":"Anantharajan","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithya","family":"Baburajendran","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L. K.","family":"Wee","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Retna","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boping","family":"Liu","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris H. Y.","family":"Tee","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perlyn Z.","family":"Kwek","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joma K.","family":"Joy","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan\u2010Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong\u2010Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substances and Functions of Natural Medicines and Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation Institute of Materia Medica Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing 100050 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klement","family":"Foo","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Keller","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre  10 Biopolis Road, Chromos, #05-01 Singapore 138670 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4715-769X","authenticated-orcid":false,"given":"Shao Q.","family":"Yao","sequence":"additional","affiliation":[{"name":"NUS Graduate School for Integrative Sciences and Engineering  21 Lower Kent Ridge, University Hall, Tan China Tuan Wing, #04-02 Singapore 119077 Singapore"},{"name":"Department of Chemistry National University of Singapore  Singapore 117543 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198810133191506"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2408149"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24275"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2922"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055717"},{"key":"e_1_2_6_6_1","first-page":"1","volume":"2018","author":"Anagnostou T.","year":"2017","journal-title":"Blood Lymphat. Cancer"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.10.21"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201707875"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201707875"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.035"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.5b00475"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2011.11.010"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.12.006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.08.017"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0624-2"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.2.442"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13248"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja4116204"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00125"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-044805"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01153"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2826"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b08536"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b08979"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6MD00017G"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201707630"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201707630"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201806037"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201806037"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201802693"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201802693"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b08366"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.925"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.8b00154"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2174"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2007.00556.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja303436y"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2015.05.005"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1817"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmb.2004.494032040358"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2018.1555587"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1582"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja208518u"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18002"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201710856"},{"key":"e_1_2_6_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201710856"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2557"},{"key":"e_1_2_6_43_1","unstructured":"\u00a0"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17997-6"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b13907"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202105383","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202105383","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202105383","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T07:00:26Z","timestamp":1693292426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202105383"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":50,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2021,7,26]]}},"alternative-id":["10.1002\/anie.202105383"],"URL":"https:\/\/doi.org\/10.1002\/anie.202105383","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.13710097.v1","asserted-by":"object"}]},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"assertion":[{"value":"2021-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}