{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T06:07:55Z","timestamp":1780380475306,"version":"3.54.1"},"reference-count":122,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007820","name":"Hangzhou Normal University","doi-asserted-by":"publisher","award":["2024JCXK06"],"award-info":[{"award-number":["2024JCXK06"]}],"id":[{"id":"10.13039\/501100007820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Analysis"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.jpha.2025.101325","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T12:00:57Z","timestamp":1746273657000},"page":"101325","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structure-based design of anticancer drugs based on \u03b2-elemene: Research foundations and development potential"],"prefix":"10.1016","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-5426","authenticated-orcid":false,"given":"Haiyi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuntao","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehuang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6734-1534","authenticated-orcid":false,"given":"Odin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jpha.2025.101325_bib1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/med.21989","article-title":"The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer","volume":"44","author":"Zou","year":"2024","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.jpha.2025.101325_bib2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00018-005-5017-3","article-title":"Antitumor effect of \u03b2-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death","volume":"62","author":"Wang","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib3","series-title":"Elemene Antitumor Drugs. Molecular Compatibility Theory and its Applications in New Drug Development and Clinical Practice","author":"Xie","year":"2022"},{"key":"10.1016\/j.jpha.2025.101325_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2022.117049","article-title":"Design, synthesis and antitumor efficacy evaluation of a series of novel \u03b2-elemene-based macrocycles","volume":"74","author":"Qi","year":"2022","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib5","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2407-11-183","article-title":"\u03b2-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis","volume":"11","author":"Liu","year":"2011","journal-title":"BMC Cancer"},{"key":"10.1016\/j.jpha.2025.101325_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2020.153184","article-title":"\u03b2-Elemene inhibits the metastasis of multidrug-resistant gastric cancer cells through miR-1323\/Cbl-b\/EGFR pathway","volume":"69","author":"Deng","year":"2020","journal-title":"Phytomedicine"},{"key":"10.1016\/j.jpha.2025.101325_bib7","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/3472745","article-title":"\u03b2-elemene restrains PTEN mRNA degradation to restrain the growth of lung cancer cells via METTL3-mediated N6 methyladenosine modification","volume":"2022","author":"Feng","year":"2022","journal-title":"J. Oncol."},{"key":"10.1016\/j.jpha.2025.101325_bib8","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.bbrc.2017.06.071","article-title":"\u03b2-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer","volume":"490","author":"Yu","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jpha.2025.101325_bib9","first-page":"770","article-title":"The effect of beta-elemene on alpha-tubulin polymerization in human hepatoma HepG2 cells","volume":"25","author":"Mao","year":"2013","journal-title":"Chin. J. Cancer Res."},{"key":"10.1016\/j.jpha.2025.101325_bib10","doi-asserted-by":"crossref","DOI":"10.3389\/pore.2021.594299","article-title":"\u03b2-elemene triggers ROS-dependent apoptosis in glioblastoma cells through suppressing STAT3 signaling pathway","volume":"27","author":"Cai","year":"2021","journal-title":"Pathol. Oncol. Res."},{"key":"10.1016\/j.jpha.2025.101325_bib11","doi-asserted-by":"crossref","first-page":"6846","DOI":"10.1111\/jcmm.14568","article-title":"Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation","volume":"23","author":"Pan","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.jpha.2025.101325_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.tice.2022.101914","article-title":"\u03b2-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1\/IGF1R pathway","volume":"79","author":"Xie","year":"2022","journal-title":"Tissue Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2019.108812","article-title":"Molecular targets of \u03b2-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review","volume":"114","author":"Zhai","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jpha.2025.101325_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-03148-8","article-title":"The mechanism of m6A methyltransferase METTL3-mediated autophagy in reversing gefitinib resistance in NSCLC cells by \u03b2-elemene","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.jpha.2025.101325_bib15","article-title":"\u03b2-elemene reverses the resistance of p53-deficient colorectal cancer cells to 5-fluorouracil by inducing pro-death autophagy and cyclin D3-dependent cycle arrest","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"10.1016\/j.jpha.2025.101325_bib16","doi-asserted-by":"crossref","DOI":"10.3390\/molecules28135253","article-title":"Combination of an oxindole derivative with (-)-\u03b2-elemene alters cell death pathways in FLT3\/ITD+ acute myeloid leukemia cells","volume":"28","author":"Alanazi","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.jpha.2025.101325_bib17","article-title":"Elemene sensitizes pancreatic cancer cells to bortezomib by enhancing proteasome inhibition via molecular patch mechanism","volume":"8","author":"Hou","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.jpha.2025.101325_bib18","article-title":"Combination of traditional Chinese medicine and epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of non-small cell lung cancer: A systematic review and meta-analysis","volume":"99","author":"Sui","year":"2020","journal-title":"Medicine (Baltim.)"},{"key":"10.1016\/j.jpha.2025.101325_bib19","article-title":"Efficacy and safety of elemene combined with chemotherapy in advanced gastric cancer: A meta-analysis","volume":"99","author":"Liu","year":"2020","journal-title":"Medicine (Baltim.)"},{"key":"10.1016\/j.jpha.2025.101325_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26195792","article-title":"Recent advances in understanding the mechanisms of elemene in reversing drug resistance in tumor cells: A review","volume":"26","author":"Tan","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.jpha.2025.101325_bib21","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.apsb.2014.10.001","article-title":"ETME, a novel \u03b2-elemene derivative, synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway","volume":"4","author":"Yu","year":"2014","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.jpha.2025.101325_bib22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.20892\/j.issn.2095-3941.2019.0156","article-title":"Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated \u03b2-elemene liposomes","volume":"17","author":"Zhai","year":"2020","journal-title":"Cancer Biol. Med."},{"key":"10.1016\/j.jpha.2025.101325_bib23","doi-asserted-by":"crossref","DOI":"10.1186\/s12951-021-01048-3","article-title":"Active targeting of orthotopic glioma using biomimetic liposomes co-loaded elemene and cabazitaxel modified by transferritin","volume":"19","author":"Li","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"10.1016\/j.jpha.2025.101325_bib24","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202207391","article-title":"Nanoheterojunction-mediated thermoelectric strategy for cancer surgical adjuvant treatment and \u03b2-elemene combination therapy","volume":"35","author":"Ji","year":"2023","journal-title":"Adv. Mater."},{"key":"10.1016\/j.jpha.2025.101325_bib25","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1002\/anie.202016330","article-title":"Stanene-based nanosheets for \u03b2-elemene delivery and ultrasound-mediated combination cancer therapy","volume":"60","author":"Chen","year":"2021","journal-title":"Angew. Chem., Int. Ed. Engl."},{"key":"10.1016\/j.jpha.2025.101325_bib26","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202170292","article-title":"Arsenene nanodots with selective killing effects and their low-dose combination with \u00df-elemene for cancer therapy","volume":"33","author":"Liu","year":"2021","journal-title":"Adv. Mater."},{"key":"10.1016\/j.jpha.2025.101325_bib27","article-title":"An investigation of the JAZ family and the CwMYC2-like protein to reveal their regulation roles in the MeJA-induced biosynthesis of \u03b2-elemene in Curcuma wenyujin","volume":"24","author":"Liu","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2024.135455","article-title":"Screening and modification of (+)-germacrene A synthase for the production of the anti-tumor drug (-)-\u03b2-elemene in engineered Saccharomyces cerevisiae","volume":"279","author":"Hu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.jpha.2025.101325_bib29","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev-biodatasci-020222-025013","article-title":"Recent developments in ultralarge and structure-based virtual screening approaches","volume":"6","author":"Gorgulla","year":"2023","journal-title":"Annu. Rev. Biomed. Data Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrg3724","article-title":"Gene expression regulation mediated through reversible m6A RNA methylation","volume":"15","author":"Fu","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.jpha.2025.101325_bib31","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1016\/j.cell.2021.03.062","article-title":"Splice site m6A methylation prevents binding of U2AF35 to inhibit RNA splicing","volume":"184","author":"Mendel","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib32","doi-asserted-by":"crossref","first-page":"D1333","DOI":"10.1093\/nar\/gkac801","article-title":"M6AREG: M6A-centered regulation of disease development and drug response","volume":"51","author":"Liu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jpha.2025.101325_bib33","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.molcel.2012.10.015","article-title":"ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility","volume":"49","author":"Zheng","year":"2013","journal-title":"Mol. Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib34","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2004880","article-title":"METTL3-mediated m6A modification is required for cerebellar development","volume":"16","author":"Wang","year":"2018","journal-title":"PLoS Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1158\/2159-8290.CD-18-0959","article-title":"The biology of m6A RNA methylation in normal and malignant hematopoiesis","volume":"9","author":"Vu","year":"2019","journal-title":"Cancer Discov."},{"key":"10.1016\/j.jpha.2025.101325_bib36","doi-asserted-by":"crossref","DOI":"10.1186\/s12943-020-01204-7","article-title":"The potential role of RNA N6-methyladenosine in cancer progression","volume":"19","author":"Wang","year":"2020","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.jpha.2025.101325_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.114839","article-title":"The roles and mechanism of m6A RNA methylation regulators in cancer immunity","volume":"163","author":"Chen","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jpha.2025.101325_bib38","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature18298","article-title":"Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex","volume":"534","author":"Wang","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.jpha.2025.101325_bib39","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.cell.2017.05.003","article-title":"The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention","volume":"169","author":"Pendleton","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib40","doi-asserted-by":"crossref","first-page":"7719","DOI":"10.1093\/nar\/gkz619","article-title":"The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112","volume":"47","author":"van Tran","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jpha.2025.101325_bib41","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nchembio.687","article-title":"N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO","volume":"7","author":"Jia","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2023.115477","article-title":"N6-methyladenosine (m6A) in cancer therapeutic resistance: Potential mechanisms and clinical implications","volume":"167","author":"Wang","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jpha.2025.101325_bib43","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.molcel.2016.03.021","article-title":"The m6A methyltransferase METTL3 promotes translation in human cancer cells","volume":"62","author":"Lin","year":"2016","journal-title":"Mol. Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib44","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/leu.2014.16","article-title":"WTAP is a novel oncogenic protein in acute myeloid leukemia","volume":"28","author":"Bansal","year":"2014","journal-title":"Leukemia"},{"key":"10.1016\/j.jpha.2025.101325_bib45","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-019-1159-2","article-title":"ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2","volume":"38","author":"Zhu","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.jpha.2025.101325_bib46","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s13105-019-00690-8","article-title":"ALKBH5 promotes invasion and metastasis of gastric cancer by decreasing methylation of the lncRNA NEAT1","volume":"75","author":"Zhang","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"10.1016\/j.jpha.2025.101325_bib47","doi-asserted-by":"crossref","DOI":"10.1186\/s12943-019-1004-4","article-title":"RNA N6-methyladenosine demethylase FTO promotes breast tumor progression through inhibiting BNIP3","volume":"18","author":"Niu","year":"2019","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.jpha.2025.101325_bib48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.canlet.2016.02.022","article-title":"RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1\u03b1 mRNA is translated","volume":"376","author":"Tanabe","year":"2016","journal-title":"Cancer Lett."},{"key":"10.1016\/j.jpha.2025.101325_bib49","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41556-018-0045-z","article-title":"Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation","volume":"20","author":"Huang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib50","article-title":"The role of m6A RNA methylation in cancer: Implication for nature products anti-cancer research","volume":"13","author":"Song","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jpha.2025.101325_bib51","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/cr.2014.3","article-title":"Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase","volume":"24","author":"Ping","year":"2014","journal-title":"Cell Res."},{"key":"10.1016\/j.jpha.2025.101325_bib52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nchembio.1432","article-title":"A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation","volume":"10","author":"Liu","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib53","doi-asserted-by":"crossref","DOI":"10.1038\/s41421-018-0019-0","article-title":"VIRMA mediates preferential m6A mRNA methylation in 3\u2019UTR and near stop codon and associates with alternative polyadenylation","volume":"4","author":"Yue","year":"2018","journal-title":"Cell Discov"},{"key":"10.1016\/j.jpha.2025.101325_bib54","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/cmdc.202000011","article-title":"Small-molecule inhibitors of METTL3, the major human epitranscriptomic writer","volume":"15","author":"Bedi","year":"2020","journal-title":"ChemMedChem"},{"key":"10.1016\/j.jpha.2025.101325_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.drudis.2023.103513","article-title":"The development of small molecules targeting methyltransferase-like 3","volume":"28","author":"Li","year":"2023","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.jpha.2025.101325_bib56","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26061499","article-title":"Anti-tumor drug discovery based on natural product \u03b2-elemene: Anti-tumor mechanisms and structural modification","volume":"26","author":"Bai","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.jpha.2025.101325_bib57","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1080\/14756366.2022.2117314","article-title":"Novel hydroxyl carboximates derived from \u03b2-elemene: Design, synthesis and anti-tumour activities evaluation","volume":"37","author":"Gao","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib58","doi-asserted-by":"crossref","DOI":"10.1080\/14756366.2023.2195991","article-title":"Design, synthesis and biological evaluation of novel histone deacetylase (HDAC) inhibitors derived from \u03b2-elemene scaffold","volume":"38","author":"Gao","year":"2023","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib59","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11262","article-title":"Insights into the activation mechanism of class I HDAC complexes by inositol phosphates","volume":"7","author":"Watson","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jpha.2025.101325_bib60","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/nchembio.2140","article-title":"Structural insights into HDAC6 tubulin deacetylation and its selective inhibition","volume":"12","author":"Miyake","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib61","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1016\/j.bmc.2006.03.041","article-title":"The synthesis and anti-proliferative effects of \u03b2-elemene derivatives with mTOR inhibition activity","volume":"14","author":"Xu","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib62","doi-asserted-by":"crossref","first-page":"101118","DOI":"10.1016\/j.jpha.2024.101118","article-title":"Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer","volume":"15","author":"Zhou","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"10.1016\/j.jpha.2025.101325_bib63","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib64","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock vina 1.2.0: New docking methods, expanded force field, and Python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib65","doi-asserted-by":"crossref","DOI":"10.1007\/s12032-013-0488-9","article-title":"Sensitization of lung cancer cells to cisplatin by \u03b2-elemene is mediated through blockade of cell cycle progression: Antitumor efficacies of \u03b2-elemene and its synthetic analogs","volume":"30","author":"Li","year":"2013","journal-title":"Med. Oncol."},{"key":"10.1016\/j.jpha.2025.101325_bib66","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1021\/acsmedchemlett.7b00035","article-title":"Antioxidant properties of novel dimers derived from natural \u03b2-elemene through inhibiting H2O2-induced apoptosis","volume":"8","author":"Chen","year":"2017","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.jpha.2025.101325_bib67","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.bmc.2008.12.040","article-title":"Synthesis and in vitro anti-proliferative activity of \u03b2-elemene monosubstituted derivatives in HeLa cells mediated through arrest of cell cycle at the G1 phase","volume":"17","author":"Sun","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib68","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1016\/j.bmcl.2014.05.078","article-title":"Design, synthesis and antioxidant activity evaluation of novel \u03b2-elemene derivatives","volume":"24","author":"Chen","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.jpha.2025.101325_bib69","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s00775-009-0502-z","article-title":"Radioactive synthesis and biodistribution study of \u03b2-elemene-99mTc(CO)3 conjugates","volume":"14","author":"Sun","year":"2009","journal-title":"J. Biol. Inorg. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib70","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.fitote.2017.05.002","article-title":"Novel hybrids of natural \u03b2-elemene bearing isopropanolamine moieties: Synthesis, enhanced anticancer profile, and improved aqueous solubility","volume":"120","author":"Chen","year":"2017","journal-title":"Fitoterapia"},{"key":"10.1016\/j.jpha.2025.101325_bib71","doi-asserted-by":"crossref","first-page":"463","DOI":"10.7164\/antibiotics.26.463","article-title":"A9145, a new adenine-containing antifungal antibiotic. I. Discovery and isolation","volume":"26","author":"Hamill","year":"1973","journal-title":"J. Antibiot. (Tokyo)"},{"key":"10.1016\/j.jpha.2025.101325_bib72","article-title":"A stapled peptide inhibitor targeting the binding interface of N6-adenosine-methyltransferase subunits METTL3 and METTL14 for cancer therapy","volume":"63","author":"Li","year":"2024","journal-title":"Angew. Chem., Int. Ed. Engl."},{"key":"10.1016\/j.jpha.2025.101325_bib73","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nrd1549","article-title":"Docking and scoring in virtual screening for drug discovery: Methods and applications","volume":"3","author":"Kitchen","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jpha.2025.101325_bib74","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.jpha.2025.101325_bib75","doi-asserted-by":"crossref","first-page":"D668","DOI":"10.1093\/nar\/gkj067","article-title":"DrugBank: A comprehensive resource for in silico drug discovery and exploration","volume":"34","author":"Wishart","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.jpha.2025.101325_bib76","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"Zinc \u2013 A free database of commercially available compounds for virtual screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib77","doi-asserted-by":"crossref","first-page":"6065","DOI":"10.1021\/acs.jcim.0c00675","article-title":"ZINC20 \u2013 A free ultralarge-scale chemical database for ligand discovery","volume":"60","author":"Irwin","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib78","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41586-021-04220-9","article-title":"Synthon-based ligand discovery in virtual libraries of over 11 billion compounds","volume":"601","author":"Sadybekov","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.jpha.2025.101325_bib79","doi-asserted-by":"crossref","first-page":"12964","DOI":"10.1039\/C6CP01555G","article-title":"Comprehensive evaluation of ten docking programs on a diverse set of protein-ligand complexes: The prediction accuracy of sampling power and scoring power","volume":"18","author":"Wang","year":"2016","journal-title":"Phys. Chem. Chem. Phys."},{"key":"10.1016\/j.jpha.2025.101325_bib80","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1006\/jmbi.1996.0897","article-title":"Development and validation of a genetic algorithm for flexible docking","volume":"267","author":"Jones","year":"1997","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jpha.2025.101325_bib81","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1002\/jcc.23905","article-title":"Dock 6: Impact of new features and current docking performance","volume":"36","author":"Allen","year":"2015","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib82","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib83","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib84","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10822-012-9570-1","article-title":"Variability in docking success rates due to dataset preparation","volume":"26","author":"Corbeil","year":"2012","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.jpha.2025.101325_bib85","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/jm020406h","article-title":"Surflex: Fully automatic flexible molecular docking using a molecular similarity-based search engine","volume":"46","author":"Jain","year":"2003","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib86","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1021\/ci2005934","article-title":"Potential and limitations of ensemble docking","volume":"52","author":"Korb","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib87","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2174\/1568026614666140929124445","article-title":"Structure-based virtual screening for drug discovery: Principles, applications and recent advances","volume":"14","author":"Lionta","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib88","article-title":"fastDRH: A webserver to predict and analyze protein-ligand complexes based on molecular docking and MM\/PB(GB)SA computation","volume":"23","author":"Wang","year":"2022","journal-title":"Brief. Bioinform."},{"key":"10.1016\/j.jpha.2025.101325_bib89","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.1016\/j.celrep.2019.02.100","article-title":"Discovery of small molecules that activate RNA methylation through cooperative binding to the METTL3-14-WTAP complex active site","volume":"26","author":"Selberg","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.jpha.2025.101325_bib90","article-title":"Discovery of METTL3 small molecule inhibitors by virtual screening of natural products","volume":"13","author":"Du","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jpha.2025.101325_bib91","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1038\/s41587-019-0224-x","article-title":"Deep learning enables rapid identification of potent DDR1 kinase inhibitors","volume":"37","author":"Zhavoronkov","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jpha.2025.101325_bib92","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.cell.2020.01.021","article-title":"A deep learning approach to antibiotic discovery","volume":"180","author":"Stokes","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.jpha.2025.101325_bib93","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41551-021-00689-x","article-title":"Accelerated antimicrobial discovery via deep generative models and molecular dynamics simulations","volume":"5","author":"Das","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.jpha.2025.101325_bib94","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s10822-013-9672-4","article-title":"Estimation of the size of drug-like chemical space based on GDB-17 data","volume":"27","author":"Polishchuk","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.jpha.2025.101325_bib95","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/s42256-023-00712-7","article-title":"ResGen is a pocket-aware 3D molecular generation model based on parallel multiscale modelling","volume":"5","author":"Zhang","year":"2023","journal-title":"Nat. Mach. Intell."},{"key":"10.1016\/j.jpha.2025.101325_bib96","article-title":"Delete: Deep lead optimization enveloped in protein pocket through unified deleting strategies and a structure-aware network","author":"Zhang","year":"2023","journal-title":"arXiv"},{"key":"10.1016\/j.jpha.2025.101325_bib97","series-title":"Proceedings of the 39th International Conference on Machine Learning (ICML), July 17\u221223, 2022","first-page":"13912","author":"Liu","year":"2022"},{"key":"10.1016\/j.jpha.2025.101325_bib98","series-title":"Proceedings of the 38th International Conference on Machine Learning (ICML), July 18\u221224","first-page":"17644","author":"Peng","year":"2021"},{"key":"10.1016\/j.jpha.2025.101325_bib99","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s43588-023-00530-2","article-title":"Learning on topological surface and geometric structure for 3D molecular generation","volume":"3","author":"Zhang","year":"2023","journal-title":"Nat. Comput. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib100","article-title":"Deep geometry handling and fragment-wise molecular 3D graph generation","author":"Zhang","year":"2024","journal-title":"arXiv"},{"key":"10.1016\/j.jpha.2025.101325_bib101","doi-asserted-by":"crossref","first-page":"22945","DOI":"10.1021\/acsomega.1c03613","article-title":"A novel scalarized scaffold hopping algorithm with graph-based variational autoencoder for discovery of JAK1 inhibitors","volume":"6","author":"Yu","year":"2021","journal-title":"ACS Omega"},{"key":"10.1016\/j.jpha.2025.101325_bib102","doi-asserted-by":"crossref","DOI":"10.1186\/s13321-021-00565-5","article-title":"Deep scaffold hopping with multimodal transformer neural networks","volume":"13","author":"Zheng","year":"2021","journal-title":"J. Cheminform."},{"key":"10.1016\/j.jpha.2025.101325_bib103","article-title":"DiffHopp: A graph diffusion model for novel drug design via scaffold hopping","author":"Torge","year":"2023","journal-title":"arXiv"},{"key":"10.1016\/j.jpha.2025.101325_bib104","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1021\/acs.jcim.9b01120","article-title":"Deep generative models for 3D linker design","volume":"60","author":"Imrie","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib105","doi-asserted-by":"crossref","first-page":"8312","DOI":"10.1039\/D0SC03126G","article-title":"SyntaLinker: Automatic fragment linking with deep conditional transformer neural networks","volume":"11","author":"Yang","year":"2020","journal-title":"Chem. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib106","series-title":"Proceedings of the 39th International Conference on Machine Learning (ICML), July 17\u221223, 2022","first-page":"9280","author":"Huang","year":"2022"},{"key":"10.1016\/j.jpha.2025.101325_bib107","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s42256-024-00815-9","article-title":"Equivariant 3D-conditional diffusion model for molecular linker design","volume":"6","author":"Igashov","year":"2024","journal-title":"Nat. Mach. Intell."},{"key":"10.1016\/j.jpha.2025.101325_bib108","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1039\/C9SC04503A","article-title":"Scaffold-based molecular design with a graph generative model","volume":"11","author":"Lim","year":"2020","journal-title":"Chem. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib109","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1021\/acs.jcim.1c00600","article-title":"MolGPT: Molecular generation using a transformer-decoder model","volume":"62","author":"Bagal","year":"2022","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.jpha.2025.101325_bib110","doi-asserted-by":"crossref","first-page":"8036","DOI":"10.1039\/D1SC00163A","article-title":"DeepFrag: A deep convolutional neural network for fragment-based lead optimization","volume":"12","author":"Green","year":"2021","journal-title":"Chem. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib111","doi-asserted-by":"crossref","first-page":"14577","DOI":"10.1039\/D1SC02436A","article-title":"Deep generative design with 3D pharmacophoric constraints","volume":"12","author":"Imrie","year":"2021","journal-title":"Chem. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib112","doi-asserted-by":"crossref","first-page":"10808","DOI":"10.1021\/acs.jmedchem.3c01009","article-title":"Fflom: A flow-based autoregressive model for fragment-to-lead optimization","volume":"66","author":"Jin","year":"2023","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib113","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-79682-4","article-title":"Transformer neural network for protein-specific de novo drug generation as a machine translation problem","volume":"11","author":"Grechishnikova","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jpha.2025.101325_bib114","doi-asserted-by":"crossref","first-page":"4852","DOI":"10.1109\/TNNLS.2022.3147790","article-title":"Geometry-based molecular generation with deep constrained variational autoencoder","volume":"35","author":"Li","year":"2021","journal-title":"IEEE Transact. Neural Networks Learn. Syst."},{"key":"10.1016\/j.jpha.2025.101325_bib115","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1039\/D1SC05976A","article-title":"Generating 3D molecules conditional on receptor binding sites with deep generative models","volume":"13","author":"Ragoza","year":"2022","journal-title":"Chem. Sci."},{"key":"10.1016\/j.jpha.2025.101325_bib116","series-title":"Proceedings of the 35th Conference on Neural Information Processing Systems (NeurIPS), December 6\u221214","author":"Luo","year":"2021"},{"key":"10.1016\/j.jpha.2025.101325_bib117","article-title":"Deep lead optimization: Leveraging generative AI for structural modification","author":"Zhang","year":"2024","journal-title":"arXiv"},{"key":"10.1016\/j.jpha.2025.101325_bib118","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1002\/(SICI)1521-3773(19991004)38:19<2894::AID-ANIE2894>3.0.CO;2-F","article-title":"\u201cScaffold-hopping\u201d by topological pharmacophore search: A contribution to virtual screening","volume":"38","author":"Schneider","year":"1999","journal-title":"Angew. Chem., Int. Ed. Engl."},{"key":"10.1016\/j.jpha.2025.101325_bib119","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1021\/acs.jmedchem.6b01437","article-title":"Recent advances in scaffold hopping","volume":"60","author":"Hu","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib120","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/minf.201000174","article-title":"Compound design by fragment-linking","volume":"30","author":"Ichihara","year":"2011","journal-title":"Mol. Inform."},{"key":"10.1016\/j.jpha.2025.101325_bib121","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.1021\/jm040031v","article-title":"Fragment-based drug discovery","volume":"47","author":"Erlanson","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.jpha.2025.101325_bib122","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.cbpa.2010.02.018","article-title":"Privileged scaffolds for library design and drug discovery","volume":"14","author":"Welsch","year":"2010","journal-title":"Curr. Opin. Chem. Biol."}],"container-title":["Journal of Pharmaceutical Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S209517792500142X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S209517792500142X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:46:17Z","timestamp":1768981577000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S209517792500142X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":122,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S209517792500142X"],"URL":"https:\/\/doi.org\/10.1016\/j.jpha.2025.101325","relation":{},"ISSN":["2095-1779"],"issn-type":[{"value":"2095-1779","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-based design of anticancer drugs based on \u03b2-elemene: Research foundations and development potential","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Analysis","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jpha.2025.101325","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V. on behalf of Xi\u2019an Jiaotong University.","name":"copyright","label":"Copyright"}],"article-number":"101325"}}