{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:47:41Z","timestamp":1790761661286,"version":"4.1.0"},"reference-count":134,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T00:00:00Z","timestamp":1614384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91856126"],"award-info":[{"award-number":["91856126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007834","name":"Natural Science Foundation of Ningbo","doi-asserted-by":"publisher","award":["2018A610410"],"award-info":[{"award-number":["2018A610410"]}],"id":[{"id":"10.13039\/100007834","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation of Ningbo University","award":["XYL20023"],"award-info":[{"award-number":["XYL20023"]}]},{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","award":["D16013"],"award-info":[{"award-number":["D16013"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+\/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical \u03b1-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure\u2013activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo, with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.<\/jats:p>","DOI":"10.3390\/ijms22052408","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T20:55:44Z","timestamp":1614459344000},"page":"2408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-4746","authenticated-orcid":false,"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamei","family":"Zou","sequence":"additional","affiliation":[{"name":"Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze","family":"Wang","sequence":"additional","affiliation":[{"name":"Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5625-5358","authenticated-orcid":false,"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-7278","authenticated-orcid":false,"given":"Shan","family":"He","sequence":"additional","affiliation":[{"name":"Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-506X","authenticated-orcid":false,"given":"C. Benjamin","family":"Naman","sequence":"additional","affiliation":[{"name":"Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejphar.2018.07.034","article-title":"Molecular targeted therapy: Treating cancer with specificity","volume":"834","author":"Lee","year":"2018","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/bs.acr.2018.02.003","article-title":"Chapter Three\u2014Acquired Resistance to Drugs Targeting Tyrosine Kinases","volume":"138","author":"Rosenzweig","year":"2018","journal-title":"Adv. Cancer. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6846","DOI":"10.1074\/jbc.272.11.6846","article-title":"Mapping of the novel protein kinase catalytic domain of dictyostelium myosin II heavy chain kinase A","volume":"272","author":"Cote","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jbior.2014.04.003","article-title":"Eukaryotic elongation factor 2 kinase, an unusual enzyme with multiple roles","volume":"55","author":"Kenney","year":"2014","journal-title":"Adv. Biol. Regul."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1042\/BST20140323","article-title":"Regulation and roles of elongation factor 2 kinase","volume":"43","author":"Proud","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S1097-2765(01)00256-8","article-title":"Crystal structure of the atypical protein kinase domain of a TRP channel with phosphotransferase activity","volume":"7","author":"Yamaguchi","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1017\/cjn.2016.336","article-title":"OS5-173 Inhibition of eEF2K as a novel therapeutic strategy in neuroblastoma and medulloblastoma","volume":"43","author":"Delaidelli","year":"2016","journal-title":"Can. J. Neurol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.15252\/emmm.201404402","article-title":"Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K","volume":"6","author":"Liu","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/15384101.2016.1254974","article-title":"Translating the anticancer properties of eEF2K","volume":"16","author":"Gassart","year":"2017","journal-title":"Cell Cycle"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15541","DOI":"10.1074\/jbc.M700702200","article-title":"Lysophosphatidic acid facilitates proliferation of colon cancer cells via induction of Kr\u00fcppel-like factor 5","volume":"282","author":"Zhang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1002\/ijc.32560","article-title":"Eukaryotic elongation factor 2 kinase promotes angiogenesis in hepatocellular carcinoma via PI3K\/Akt and STAT3","volume":"146","author":"Zhou","year":"2020","journal-title":"Int. J. Cancer."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41970","DOI":"10.1074\/jbc.M302403200","article-title":"Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2","volume":"278","author":"Horman","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s00109-020-01917-8","article-title":"Eukaryotic elongation factor-2 kinase (eEF2K) signaling in tumor and microenvironment as a novel molecular target","volume":"98","author":"Karakas","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s10495-013-0927-2","article-title":"Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic cancer cells","volume":"19","author":"Ashour","year":"2014","journal-title":"Apoptosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.cellsig.2016.01.005","article-title":"Elongation factor 2 kinase promotes cell survival by inhibiting protein synthesis without inducing autophagy","volume":"28","author":"Moore","year":"2016","journal-title":"Cell Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1093\/emboj\/20.16.4370","article-title":"Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase","volume":"20","author":"Wang","year":"2001","journal-title":"EMBO J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1089\/ars.2010.3699","article-title":"Regulation of translation by hydrogen peroxide","volume":"15","author":"Grant","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/sj.emboj.7600102","article-title":"Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation","volume":"23","author":"Spahn","year":"2004","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/MCB.01270-12","article-title":"Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase","volume":"33","author":"Hizli","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"ra40","DOI":"10.1126\/scisignal.2002718","article-title":"Coupled activation and degradation of eEF2K regulates protein synthesis in response to genotoxic stress","volume":"5","author":"Kruiswijk","year":"2012","journal-title":"Sci. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.bbagrm.2014.11.002","article-title":"Stress-mediated translational control in cancer cells","volume":"1849","author":"Leprivier","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.15252\/emmm.201404683","article-title":"eEF2K-a new target in breast cancers with combined inactivation of p53 and PTEN","volume":"6","author":"Russnes","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"16619","DOI":"10.18632\/oncotarget.7672","article-title":"FOXM1 regulates expression of eukaryotic elongation factor 2 kinase and promotes proliferation, invasion and tumorgenesis of human triple negative breast cancer cells","volume":"7","author":"Hamurcu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tice.2018.05.014","article-title":"Eukaryotic elongation factors 2 promotes tumor cell proliferation and correlates with poor prognosis in ovarian cancer","volume":"53","author":"Shi","year":"2018","journal-title":"Tissue Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11641","DOI":"10.18632\/oncotarget.14264","article-title":"MicroRNA 603 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting elongation factor 2 kinase","volume":"8","author":"Bayraktar","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.lungcan.2018.07.027","article-title":"Elongation factor-2 kinase (eEF-2K) expression is associated with poor patient survival and promotes proliferation, invasion and tumor growth of lung cancer","volume":"124","author":"Bircan","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.cell.2013.04.055","article-title":"The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation","volume":"153","author":"Leprivier","year":"2013","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tibs.2013.01.004","article-title":"Nutrient signaling to mTOR and cell growth","volume":"38","author":"Jewell","year":"2013","journal-title":"Trends Biochem. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/334170a0","article-title":"Phosphorylation of elongation factor 2 by EF-2 kinase affects rate of translation","volume":"334","author":"Ryazanov","year":"1988","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1042\/BST20130036","article-title":"mTORC1 regulates the efficiency and cellular capacity for protein synthesis","volume":"41","author":"Proud","year":"2013","journal-title":"Biochem. Soc. Trans."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BJ20070024","article-title":"Signalling to translation: How signal transduction pathways control the protein synthetic machinery","volume":"403","author":"Proud","year":"2007","journal-title":"Biochem. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nature13896","article-title":"mTORC1-mediated translational elongation limits intestinal tumour initiation and growth","volume":"517","author":"Faller","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1128\/MCB.26.10.3955-3965.2006","article-title":"Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells","volume":"26","author":"Connolly","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1128\/MCB.01457-14","article-title":"Elongation Factor 2 Kinase Is Regulated by Proline Hydroxylation and Protects Cells during Hypoxia","volume":"35","author":"Moore","year":"2015","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6293","DOI":"10.1038\/onc.2016.166","article-title":"eEF-2 kinase is a critical regulator of Warburg effect through controlling PP2A-A synthesis","volume":"35","author":"Cheng","year":"2016","journal-title":"Oncogene"},{"key":"ref_37","first-page":"1284","article-title":"Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism","volume":"8","author":"Helmlinger","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7175","DOI":"10.4049\/jimmunol.180.11.7175","article-title":"Tumor-secreted lactic acid promotes IL-23\/IL-17 proinflammatory pathway","volume":"180","author":"Shime","year":"2008","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13444","DOI":"10.1021\/bi026494p","article-title":"Regulation of elongation factor-2 kinase by pH","volume":"41","author":"Dorovkov","year":"2002","journal-title":"Biochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1128\/MCB.00012-15","article-title":"Molecular mechanism for the control of eukaryotic elongation factor 2 kinase by pH: Role in cancer cell survival","volume":"35","author":"Xie","year":"2015","journal-title":"Mol. Cell. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1007\/s00384-011-1217-5","article-title":"Polymorphisms of Caspase 8 and Caspase 9 gene and colorectal cancer susceptibility and prognosis","volume":"26","author":"Theodoropoulos","year":"2011","journal-title":"Int. J. Colorectal. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbrc.2008.09.126","article-title":"Protein tyrosine kinase p56lck-deficiency confers hypersusceptibility to rho-fluorophenylalanine (pFPhe)-induced apoptosis by augmenting mitochondrial apoptotic pathway in human Jurkat T cells","volume":"377","author":"Park","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2008.03.036","article-title":"TNF-alpha induces two distinct caspase-8 activation pathways","volume":"133","author":"Wang","year":"2008","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1111\/j.1582-4934.2009.00777.x","article-title":"DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas","volume":"14","author":"Bellail","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bbrc.2011.09.038","article-title":"Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression","volume":"414","author":"Zhang","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/sj.cdd.4401088","article-title":"The role of mitochondrial factors in apoptosis: A Russian roulette with more than one bullet","volume":"9","author":"Saelens","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Tekedereli, I., Alpay, S.N., Tavares, C.D.J., Cobanoglu, Z.E., Kaoud, T.S., Sahin, I., Sood, A.K., Lopez-Berestein, G., Dalby, K.N., and Ozpolat, B. (2012). Targeted Silencing of Elongation Factor 2 Kinase Suppresses Growth and Sensitizes Tumors to Doxorubicin in an Orthotopic Model of Breast Cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041171"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/sj.bjc.6690012","article-title":"Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer","volume":"79","author":"Parmer","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1002\/pmic.200600365","article-title":"Identification of G2\/M targets for the MAP kinase pathway by functional proteomics","volume":"6","author":"Roberts","year":"2010","journal-title":"Proteomics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1083\/jcb.107.3.993","article-title":"Long-lasting and rapid calcium changes during mitosis","volume":"107","author":"Ratan","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/bbrc.1998.8086","article-title":"The role of calcium in the cell cycle: Facts and hypotheses","volume":"244","author":"Santella","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/S0898-6568(03)00038-X","article-title":"Cyclic AMP inhibits translation of cyclin D3 in T lymphocytes at the level of elongation by inducing eEF2-phosphorylation","volume":"15","author":"Gutzkow","year":"2003","journal-title":"Cell. Signal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1042\/BJ20111530","article-title":"Identification of autophosphorylation sites in eukaryotic elongation factor-2 kinase","volume":"442","author":"Wang","year":"2012","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/emboj.2008.39","article-title":"cdc2\u2013cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner","volume":"27","author":"Smith","year":"2008","journal-title":"EMBO J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/CCO.0000000000000159","article-title":"Cell cycle control as a promising target in melanoma","volume":"27","author":"Lee","year":"2015","journal-title":"Curr. Opin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41577-020-0300-y","article-title":"Immunomodulation by anticancer cell cycle inhibitors","volume":"20","author":"Petroni","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cell.2007.12.018","article-title":"Autophagy in the Pathogenesis of Disease","volume":"132","author":"Levine","year":"2008","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nrc1692","article-title":"The role of autophagy in cancer development and response to therapy","volume":"5","author":"Kondo","year":"2005","journal-title":"Nat. Rev. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Li, H., Ren, X., Niu, T., Hait, W.N., and Yang, J. (2010). Cytoprotective Effect of the Elongation Factor-2 Kinase-Mediated Autophagy in Breast Cancer Cells Subjected to Growth Factor Inhibition. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009715"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s12276-020-0455-4","article-title":"Autophagy as a decisive process for cell death","volume":"52","author":"Jung","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5037","DOI":"10.1158\/1078-0432.CCR-15-0490","article-title":"Autophagy, Metabolism, and Cancer","volume":"21","author":"White","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrc3262","article-title":"Deconvoluting the context-dependent role for autophagy in cancer","volume":"12","author":"White","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1158\/0008-5472.CAN-10-2889","article-title":"eEF-2 kinase dictates cross-talk between autophagy and apoptosis induced by Akt Inhibition, thereby modulating cytotoxicity of novel Akt inhibitor MK-2206","volume":"71","author":"Cheng","year":"2011","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.2147\/DDDT.S169952","article-title":"Inhibiting eEF-2 kinase-mediated autophagy enhanced the cytocidal effect of AKT inhibitor on human nasopharyngeal carcinoma","volume":"12","author":"Zhao","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"393","DOI":"10.4161\/auto.5.3.7762","article-title":"A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses","volume":"5","author":"Py","year":"2009","journal-title":"Autophagy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/sj.cdd.4402296","article-title":"A pharmacoproteomic approach implicates eukaryotic elongation factor 2 kinase in ER stress-induced cell death","volume":"15","author":"Boyce","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1158\/0008-5472.CAN-08-2872","article-title":"Silencing of elongation factor-2 kinase potentiates the effect of 2-deoxy-D-glucose against human glioma cells through blunting of autophagy","volume":"69","author":"Wu","year":"2009","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.4161\/auto.29164","article-title":"Silencing of EEF2K (eukaryotic elongation factor-2 kinase) reveals AMPK-ULK1-dependent autophagy in colon cancer cells","volume":"10","author":"Xie","year":"2014","journal-title":"Autophagy"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41419-019-1431-6","article-title":"CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT\/NF-\u03baB pathway in colorectal cancer","volume":"10","author":"Chen","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2019.02.015","article-title":"Lenvatinib induces death of human hepatocellular carcinoma cells harboring an activated FGF signaling pathway through inhibition of FGFR\u2013MAPK cascades","volume":"513","author":"Hoshi","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.radonc.2017.04.001","article-title":"eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma","volume":"124","author":"Zhu","year":"2017","journal-title":"Radiother. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.3892\/ol.2015.4072","article-title":"MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma","volume":"11","author":"Shi","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1111\/jcmm.12361","article-title":"Elongation factor-2 kinase regulates TG2\/\u03b21 integrin\/Src\/uPAR pathway and epithelial-mesenchymal transition mediating pancreatic cancer cells invasion","volume":"18","author":"Ashour","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.1158\/1078-0432.CCR-17-1959","article-title":"Dual Suppressive Effect of miR-34a on the FOXM1\/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion","volume":"24","author":"Bayraktar","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1002\/ijc.31210","article-title":"Eukaryotic elongation factor 2 kinase upregulates the expression of proteins implicated in cell migration and cancer cell metastasis","volume":"142","author":"Xie","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1016\/j.jmb.2018.05.033","article-title":"Structural Dynamics of the Activation of Elongation Factor 2 Kinase by Ca(2+)-Calmodulin","volume":"430","author":"Will","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1073\/pnas.94.10.4884","article-title":"Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase","volume":"94","author":"Alexey","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1271\/bbb.64.919","article-title":"Identification and Characterization of a Potent Antibacterial Agent, NH125 against Drug-resistant Bacteria","volume":"64","author":"Yamamoto","year":"2000","journal-title":"Biosci. Biotech. Biochem."},{"key":"ref_81","first-page":"6894","article-title":"Identification and Characterization of an Inhibitor of Eukaryotic Elongation Factor 2 Kinase against Human Cancer Cell Lines","volume":"63","author":"Arora","year":"2003","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"43951","DOI":"10.1074\/jbc.M111.301291","article-title":"1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2)","volume":"286","author":"Chen","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1021\/bi201787p","article-title":"Investigating the kinetic mechanism of inhibition of elongation factor 2 kinase by NH125: Evidence of a common in vitro artifact","volume":"51","author":"Devkota","year":"2012","journal-title":"Biochemistry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1016\/S0968-0896(02)00160-8","article-title":"TX-1123: An antitumor 2-hydroxyarylidene-4-cyclopentene-1,3-dione as a protein tyrosine kinase inhibitor having low mitochondrial toxicity","volume":"10","author":"Hori","year":"2002","journal-title":"Bioorg. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jphs.2018.04.006","article-title":"Mechanisms underlying the relaxation by A484954, a eukaryotic elongation factor 2 kinase inhibitor, in rat isolated mesenteric artery","volume":"137","author":"Tomoko","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4910","DOI":"10.1016\/j.bmc.2014.06.050","article-title":"Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors","volume":"22","author":"Edupuganti","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"112505","DOI":"10.1016\/j.ejmech.2020.112505","article-title":"Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells","volume":"204","author":"Liu","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1039\/a809131e","article-title":"Synthesis and characterization of novel 1,3-selenazine derivatives. BF3\u00b7Et2O-assisted reaction of primary selenoamides with \u03b1,\u03b2-unsaturated ketones","volume":"1","author":"Koketsu","year":"1999","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0304-4165(00)00061-1","article-title":"Novel compounds, \u20181,3-selenazine derivatives\u2019 as specific inhibitors of eukaryotic elongation factor-2 kinase","volume":"1475","author":"Cho","year":"2000","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1016\/j.bmc.2009.02.049","article-title":"PLC, Phospholipase C, PLC-gamma, The identification of novel PLC-\u03b3 inhibitors using virtual high throughput screening","volume":"17","author":"Reynisson","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1039\/C3MD00290J","article-title":"The effect of a thieno[2,3-b]pyridine PLC-\u03b3 inhibitor on the proliferation, morphology, migration and cell cycle of breast cancer cells","volume":"5","author":"Leung","year":"2014","journal-title":"MedChemComm"},{"key":"ref_92","unstructured":"Ostanin, K., and Hunsaker, T. (2008). Enzyme Assay and Use Thereof. (7338775B1), US Patent, Current Assignee: Myrexis Inc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1016\/j.bmcl.2010.02.005","article-title":"Inhibition of eEF2-K by thieno[2,3-b]pyridine analogues","volume":"20","author":"Lockman","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ejmech.2017.11.065","article-title":"Design, synthesis and structure\u2013activity relationship of a focused library of \u03b2-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing mechanisms in breast cancer","volume":"143","author":"Guo","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e12402","DOI":"10.1111\/cpr.12402","article-title":"Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer","volume":"51","author":"Sun","year":"2018","journal-title":"Cell Prolif."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.tips.2007.07.003","article-title":"Rottlerin: An inappropriate and ineffective inhibitor of PKC\u03b4","volume":"28","author":"Soltoff","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1158\/1541-7786.MCR-06-0229","article-title":"Tissue transglutaminase inhibits autophagy in pancreatic cancer cells","volume":"5","author":"Akar","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_98","first-page":"273","article-title":"Protein kinase C delta is a prosurvival factor in human breast tumor cell lines","volume":"2","author":"McCracken","year":"2003","journal-title":"Mol. Cancer Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2012.02.003","article-title":"Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC \u03b4-independent mechanism","volume":"197","author":"Lim","year":"2012","journal-title":"Chem. Biol. Interact."},{"key":"ref_100","first-page":"780","article-title":"Altered protein kinase C (PKC) isoforms in non-small cell lung cancer cells: PKCdelta promotes cellular survival and chemotherapeutic resistance","volume":"63","author":"Clark","year":"2003","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1046\/j.1365-2141.2003.04368.x","article-title":"Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis","volume":"121","author":"Ni","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0014-5793(94)80121-5","article-title":"Elongation factor-2 kinase: Effective inhibition by the novel protein kinase inhibitor rottlerin and relative insensitivity towards staurosporine","volume":"338","author":"Gschwendt","year":"1994","journal-title":"FEBS Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"37986","DOI":"10.1074\/jbc.M105073200","article-title":"Rottlerin Is a Mitochondrial Uncoupler That Decreases Cellular ATP Levels and Indirectly Blocks Protein Kinase C\u03b4 Tyrosine Phosphorylation","volume":"276","author":"Soltoff","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/j.1742-7843.2007.00143.x","article-title":"Rottlerin induces calcium influx and protein degradation in cultured lenses independent of effects on protein kinase C delta","volume":"101","author":"Xu","year":"2007","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_105","first-page":"327","article-title":"Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in malignant glioma cells","volume":"8","author":"Parmer","year":"1997","journal-title":"Cell Growth Differ."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"G63","DOI":"10.1152\/ajpgi.00257.2009","article-title":"Rottlerin stimulates apoptosis in pancreatic cancer cells through interactions with proteins of the Bcl-2 family","volume":"298","author":"Ohno","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/cbf.968","article-title":"Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DT-diaphorase in different tissues of mice: A possible mechanism of action","volume":"20","author":"Mansour","year":"2002","journal-title":"Cell Biochem. Funct."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1080\/01635581.2010.509832","article-title":"Review on molecular and therapeutic potential of thymoquinone in cancer","volume":"62","author":"Banerjee","year":"2010","journal-title":"Nutr. Cancer"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"51907","DOI":"10.18632\/oncotarget.17206","article-title":"Thymoquinone, as an anticancer molecule: From basic research to clinical investigation","volume":"8","author":"Tania","year":"2017","journal-title":"Oncotarget"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.18632\/oncotarget.27426","article-title":"Thymoquinone induces apoptosis and DNA damage in 5-Fluorouracil-resistant colorectal cancer stem\/progenitor cells","volume":"11","author":"Ballout","year":"2020","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"AlGhamdi, A.A., Mohammed, M.R.S., Zamzami, M.A., Al-Malki, A.L., Qari, M.H., Khan, M.I., and Choudhry, H. (2020). Untargeted metabolomics identifies key metabolic pathways altered by thymoquinone in leukemic cancer cells. Nutrients, 12.","DOI":"10.3390\/nu12061792"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mrfmmm.2010.10.007","article-title":"Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells","volume":"706","author":"Zhu","year":"2011","journal-title":"Mutat. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/0929867326666191011143642","article-title":"Targeting inflammatory mediators: An anticancer mechanism of thymoquinone action","volume":"28","author":"Akter","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.jsps.2019.09.008","article-title":"Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive\/anticancer agent: Chemistry and biological effects","volume":"27","author":"Ahmad","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s10549-018-4847-2","article-title":"Thymoquinone inhibits cell proliferation, migration, and invasion by regulating the elongation factor 2 kinase (eEF-2K) signaling axis in triple-negative breast cancer","volume":"171","author":"Kabil","year":"2018","journal-title":"Breast Cancer Res. Ther."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2174\/157340605774598135","article-title":"Isolation of bioactive natural products from myxomycetes","volume":"1","author":"Ishibashi","year":"2005","journal-title":"Med. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Li, T., Wang, N., Zhang, T., Zhang, B., Sajeevan, T.P., Joseph, V., Armstrong, L., He, S., Yan, X., and Naman, C.B. (2019). A systematic review of recently reported marine derived natural product kinase inhibitors. Mar. Drugs, 17.","DOI":"10.3390\/md17090493"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1039\/D0NP00011F","article-title":"Natural products targeting the elongation phase of eukaryotic protein biosynthesis","volume":"37","author":"Bronstrup","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/cbic.201200522","article-title":"The marine polyketide myriaporone 3\/4 stalls translation by targeting the elongation phase","volume":"14","author":"Muthukumar","year":"2013","journal-title":"Chembiochem"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0040-4020(01)01170-X","article-title":"Leptosins M-N1, cytotoxic metabolites from a Leptosphaeria species separated from a marine alga. Structure determination and biological activities","volume":"58","author":"Yamada","year":"2002","journal-title":"Tetrahedron"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"70595","DOI":"10.18632\/oncotarget.19883","article-title":"Calyxin Y sensitizes cisplatin-sensitive and resistant hepatocellular carcinoma cells to cisplatin through apoptotic and autophagic cell death via SCF \u03b2TrCP-mediated eEF2K degradation","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ejmech.2017.12.046","article-title":"Design, synthesis, and biological evaluation of polo-like kinase 1\/eukaryotic elongation factor 2 kinase (PLK1\/EEF2K) dual inhibitors for regulating breast cancer cells apoptosis and autophagy","volume":"144","author":"Pan","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2880","DOI":"10.1080\/14786419.2019.1596099","article-title":"New sorbicillinoid derivatives with GLP-1R and eEF2K affinities from a sponge-derived fungus Penicillium chrysogenum 581F1","volume":"34","author":"Cao","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_124","first-page":"4010","article-title":"Disruption of the EF-2 kinase\/Hsp90 protein complex: A possible mechanism to inhibit glioblastoma by geldanamycin","volume":"61","author":"Yang","year":"2001","journal-title":"Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Khaledian, B., Taguchi, A., Shin-Ya, K., Kondo-Ida, L., Kagaya, N., Suzuki, M., Kajino, T., Yamaguchi, T., Shimada, Y., and Takahashi, T. (2021). Inhibition of heat shock protein 90 destabilizes receptor tyrosine kinase ROR1 in lung adenocarcinoma. Cancer Sci., in press.","DOI":"10.1111\/cas.14786"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/cbdd.13486","article-title":"Spotlight on 17-AAG as an Hsp90 inhibitor for molecular targeted cancer treatment","volume":"93","author":"Talaei","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/ddr.21673","article-title":"Prospects of multitarget drug designing strategies by linking molecular docking and molecular dynamics to explore the protein\u2013Ligand recognition process","volume":"81","author":"Sivakumar","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fendo.2012.00158","article-title":"Glucagon-like peptide-1 receptor overexpression in cancer and its impact on clinical applications","volume":"3","author":"Korner","year":"2012","journal-title":"Front. Endocrinol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/ijc.24500","article-title":"Autophagy-A double-edged sword in oncology","volume":"125","author":"Apel","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4331\/wjbc.v3.i6.110","article-title":"Mechanisms mediating the effects of alcohol and HIV anti-retroviral agents on mTORC1, mTORC2 and protein synthesis in myocytes","volume":"3","author":"Kazi","year":"2012","journal-title":"World J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/jcb.21882","article-title":"Lopinavir impairs protein synthesis and induces eEF2 phosphorylation via the activation of AMP-activated protein kinase","volume":"105","author":"Brown","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_132","first-page":"22","article-title":"Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines","volume":"7","author":"Xu","year":"2020","journal-title":"Mil. Med. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"481","DOI":"10.2353\/ajpath.2010.090836","article-title":"Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway","volume":"177","author":"Khan","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jep.2015.02.025","article-title":"Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma","volume":"164","author":"Wang","year":"2015","journal-title":"J. Ethnopharmacol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2408\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:30:14Z","timestamp":1760160614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,27]]},"references-count":134,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052408"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052408","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,27]]}}}