{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:01:37Z","timestamp":1783645297607,"version":"3.55.0"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.ejmech.2020.112896","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T21:12:27Z","timestamp":1601586747000},"page":"112896","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"special_numbering":"C","title":["Discovery of lysosome-targeted covalent anticancer agents based on isosteviol skeleton"],"prefix":"10.1016","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8175-6293","authenticated-orcid":false,"given":"Jun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaopeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiguo","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-1811","authenticated-orcid":false,"given":"Hongxiang","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2020.112896_bib1","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1039\/C7CS00220C","article-title":"Structure-based design of targeted covalent inhibitors","volume":"47","author":"Lonsdale","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.ejmech.2020.112896_bib2","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/cbic.201900674","article-title":"Covalent small molecules as enabling platforms for drug discovery","volume":"21","author":"Campos","year":"2020","journal-title":"Chembiochem"},{"key":"10.1016\/j.ejmech.2020.112896_bib3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/acs.jmedchem.6b00788","article-title":"Covalent modifiers: a chemical perspective on the reactivity of \u03b1, \u03b2-unsaturated carbonyls with thiols via hetero-Michael addition reactions","volume":"60","author":"Jackson","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib4","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/nchembio.1582","article-title":"A\u00a0road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors","volume":"10","author":"Lanning","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2020.112896_bib5","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1021\/acs.jmedchem.7b01514","article-title":"Regio-and stereospecific synthesis of oridonin D-ring aziridinated analogues for the treatment of triple-negative breast cancer via mediated irreversible covalent warheads","volume":"61","author":"Ding","year":"2018","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.drup.2015.11.004","article-title":"Lysosomes as mediators of drug resistance in cancer","volume":"24","author":"Zhitomirsky","year":"2016","journal-title":"Drug Resist. Updates"},{"key":"10.1016\/j.ejmech.2020.112896_bib7","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ejmech.2017.05.050","article-title":"Design, synthesis and biological evaluation of nitrogen-containing macrocyclic bisbibenzyl derivatives as potent anticancer agents by targeting the lysosome","volume":"136","author":"Sun","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib8","doi-asserted-by":"crossref","first-page":"15584","DOI":"10.1002\/anie.201906284","article-title":"Guiding drugs to target-harboring organelles: stretching drug-delivery to a higher level of resolution","volume":"58","author":"Louzoun-Zada","year":"2019","journal-title":"Angew. Chem., Int. Ed. Engl."},{"key":"10.1016\/j.ejmech.2020.112896_bib9","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1002\/anie.200250653","article-title":"Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change","volume":"42","author":"Bae","year":"2003","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2020.112896_bib10","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.18632\/oncotarget.2732","article-title":"Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance","volume":"6","author":"Zhitomirsky","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.ejmech.2020.112896_bib11","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/med.21474","article-title":"Strategies to diversify natural products for drug discovery","volume":"38","author":"Li","year":"2018","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2020.112896_bib12","doi-asserted-by":"crossref","first-page":"7166","DOI":"10.1021\/acs.jmedchem.7b00951","article-title":"Discovery of potent orally active protease-activated receptor 1 (PAR1) antagonists based on andrographolide","volume":"60","author":"Liu","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib13","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.3390\/ijms17091395","article-title":"Oridonin, a promising ent-kaurane diterpenoid lead compound","volume":"17","author":"Li","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2020.112896_bib14","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3390\/molecules24040678","article-title":"Bioactivity profile of the diterpene isosteviol and its derivatives","volume":"24","author":"Ullah","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2020.112896_bib15","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.ejmech.2018.07.052","article-title":"Diterpenoid lead stevioside and its hydrolysis products steviol and isosteviol: biological activity and structural modification","volume":"156","author":"Wang","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib16","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1021\/ol400385w","article-title":"Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol","volume":"15","author":"Hutt","year":"2013","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2020.112896_bib17","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1016\/j.bmcl.2014.03.004","article-title":"Synthesis and cytotoxic activity of nitric oxide-releasing isosteviol derivatives","volume":"24","author":"Wang","year":"2014","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2020.112896_bib18","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1021\/acs.jmedchem.5b00208","article-title":"ent-Kaurane diterpenoids from Chinese liverworts and their antitumor activities through michael addition as detected in situ by a fluorescence probe","volume":"58","author":"Lin","year":"2015","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib19","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/cmdc.201300409","article-title":"Design, synthesis and structure-activity relationships studies on the D ring of the natural product triptolide","volume":"9","author":"Xu","year":"2014","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2020.112896_bib20","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1021\/acs.jmedchem.5b01082","article-title":"Targeting drug resistance in EGFR with covalent inhibitors: a structure-based design approach","volume":"58","author":"Engel","year":"2015","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.toxlet.2013.07.007","article-title":"Alpha, beta-unsaturated lactones 2-furanone and 2-pyrone induce cellular DNA damage, formation of topoisomerase I- and II-DNA complexes and cancer cell death","volume":"222","author":"Calder\u00f3n-Monta\u00f1o","year":"2013","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.ejmech.2020.112896_bib22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1071\/C97213","article-title":"Oxidative decarboxylation of podocarpic acid derivatives","volume":"51","author":"Cambie","year":"1998","journal-title":"Aust. J. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib23","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1039\/C8CC00865E","article-title":"A\u00a0chiral organic base catalyst with halogen-bonding-donor functionality: asymmetric Mannich reactions of malononitrile with N-Boc aldimines and ketimines","volume":"54","author":"Kuwano","year":"2018","journal-title":"Chem. Commun."},{"key":"10.1016\/j.ejmech.2020.112896_bib24","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.2174\/092986710793205426","article-title":"Prodrug design to improve pharmacokinetic and drug delivery properties: challenges to the discovery scientists","volume":"17","author":"Jana","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib25","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2013.12.022","article-title":"Molecular mechanism of autophagic membrane-scaffold assembly and disassembly","volume":"156","author":"Kaufmann","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2020.112896_bib26","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/ncb3043","article-title":"Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization","volume":"16","author":"Sargeant","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ejmech.2020.112896_bib27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/ncb2171","article-title":"Stat3 controls lysosomal-mediated cell death in\u00a0vivo","volume":"13","author":"Kreuzaler","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ejmech.2020.112896_bib28","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1101\/gad.17558811","article-title":"The dynamic nature of autophagy in cancer","volume":"25","author":"Kimmelman","year":"2011","journal-title":"Genes Dev."},{"key":"10.1016\/j.ejmech.2020.112896_bib29","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1021\/acs.jmedchem.8b00241","article-title":"Natural product micheliolide (MCL) irreversibly activates pyruvate kinase M2 and suppresses leukemia","volume":"61","author":"Li","year":"2018","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2020.112896_bib30","doi-asserted-by":"crossref","first-page":"10488","DOI":"10.1021\/acs.jmedchem.8b01018","article-title":"Tanshinone-IIA-based analogues of imidazole alkaloid act as potent inhibitors to block breast cancer invasion and metastasis in\u00a0vivo","volume":"61","author":"Wu","year":"2018","journal-title":"J.\u00a0Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523420308680?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523420308680?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T14:22:18Z","timestamp":1759328538000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523420308680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":30,"alternative-id":["S0223523420308680"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112896","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of lysosome-targeted covalent anticancer agents based on isosteviol skeleton","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2020.112896","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"112896"}}