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The current approaches for the treatment of this syndrome are not always effective and well established. Drug repurposing or repositioning consists of the investigation of pharmacological components that are already available or in clinical trials for certain diseases and explores if they can be used for new indications. Its advantages comparing to de novo drugs development are the reduced amount of time spent and costs. In this paper, we selected drugs already available or in clinical trials for non-cachexia indications and that are related to the pathways and molecular components involved in the different phenotypes of cancer cachexia syndrome. Thus, we introduce known drugs as possible candidates for drug repurposing in the treatment of cancer-induced cachexia.<\/jats:p>","DOI":"10.3390\/ph14111084","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Towards Drug Repurposing in Cancer Cachexia: Potential Targets and Candidates"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-524X","authenticated-orcid":false,"given":"Joana M. O.","family":"Santos","sequence":"first","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Alexandra C.","family":"Costa","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"T\u00e2nia R.","family":"Dias","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer\u2013Regional Nucleus of the North (Liga Portuguesa Contra o Cancro\u2013N\u00facleo Regional do Norte), 4200-177 Porto, Portugal"}]},{"given":"Setareh","family":"Satari","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"}]},{"given":"Maria Paula","family":"Costa e Silva","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Palliative Care Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui M. Gil","family":"da Costa","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Postgraduate Programme in Adult Health (PPGSAD), Department of Morphology, Federal University of Maranh\u00e3o (UFMA), S\u00e3o Lu\u00eds 65080-805, Brazil"},{"name":"LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-8373","authenticated-orcid":false,"given":"Rui","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)\/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal"},{"name":"Faculty of Medicine, University of Porto (FMUP), 4200-319 Porto, Portugal"},{"name":"Research Department of the Portuguese League against Cancer\u2013Regional Nucleus of the North (Liga Portuguesa Contra o Cancro\u2013N\u00facleo Regional do Norte), 4200-177 Porto, Portugal"},{"name":"Virology Service, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"},{"name":"Biomedical Research Center (CEBIMED), Faculty of Health Sciences, Fernando Pessoa University, 4249-004 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/jcsm.12528","article-title":"Cancer cachexia and its pathophysiology: Links with sarcopenia, anorexia and asthenia","volume":"11","author":"Santos","year":"2020","journal-title":"J. Cachex Sarcopenia Muscle"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: An international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1200\/JCO.20.00611","article-title":"Management of Cancer Cachexia: ASCO Guideline","volume":"38","author":"Roeland","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_4","first-page":"434","article-title":"Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer","volume":"1871","author":"Scapozza","year":"2019","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"17105","DOI":"10.1038\/nrdp.2017.105","article-title":"Cancer-associated cachexia","volume":"4","author":"Baracos","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Argiles","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Porporato, P. (2016). Understanding cachexia as a cancer metabolism syndrome. Oncogenesis, 5.","DOI":"10.1038\/oncsis.2016.3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.7150\/ijbs.24612","article-title":"Review of Drug Repositioning Approaches and Resources","volume":"14","author":"Xue","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_9","unstructured":"Roy, K. (2019). In Silico Databases and Tools for Drug Repurposing. In Silico Drug Design, Academic Press. Chapter 24."},{"key":"ref_10","first-page":"D1006","article-title":"The IUPHAR\/BPS Guide to pharmacology in 2020: Extending immunopharmacology content and introducing the IUPHAR\/MMV Guide to malaria pharmacology","volume":"48","author":"Armstrong","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: A major update to the DrugBank database for 2018","volume":"46","author":"Wishart","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_12","first-page":"7960","article-title":"Therapeutic strategies against cancer cachexia","volume":"29","author":"Stemmler","year":"2019","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_13","first-page":"707","article-title":"Efficacy and Safety of Adalimumab Biosimilars: Current Critical Clinical Data in Rheumatoid Arthritis","volume":"12","author":"Lu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1517\/14740338.4.4.637","article-title":"Adalimumab: A review of side effects","volume":"4","author":"Scheinfeld","year":"2005","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.phrs.2008.02.006","article-title":"Effect of anti-tumor necrosis factor-\u03b1 therapies on body mass index in patients with psoriasis","volume":"57","author":"Saraceno","year":"2008","journal-title":"Pharmacol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s40259-020-00416-z","article-title":"Certolizumab Pegol: A Review in Moderate to Severe Plaque Psoriasis","volume":"34","author":"Lee","year":"2020","journal-title":"BioDrugs"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/14712598.2012.645533","article-title":"Certolizumab pegol for the treatment of rheumatoid arthritis","volume":"12","author":"Horton","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_18","unstructured":"Goel, P., and Gerriets, V. (2021). Chloroquine, StatPearls Publishing LLC."},{"key":"ref_19","unstructured":"Gupta, A., and Preuss, C.V. (2021). Inamrinone, StatPearls Publishing LLC."},{"key":"ref_20","first-page":"E491","article-title":"Amrinone prevents muscle protein wasting during chronic sepsis","volume":"268","author":"Jurasinski","year":"1995","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/mus.22066","article-title":"Phosphodiesterase-4 inhibition reduces proteolysis and atrogenes expression in rat skeletal muscles","volume":"44","author":"Lira","year":"2011","journal-title":"Muscle Nerve"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1016\/S1470-2045(16)30581-2","article-title":"Pomalidomide for symptomatic Kaposi\u2019s sarcoma","volume":"17","author":"Burki","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.2147\/DDDT.S115456","article-title":"Pomalidomide in the treatment of multiple myeloma: Design, development and place in therapy","volume":"11","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1182\/blood-2013-05-484782","article-title":"Pomalidomide","volume":"122","author":"Lacy","year":"2013","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, J.-Y., Cao, H.-Y., Liu, P., Cheng, G.-H., and Sun, M.-Y. (2014). Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/872139"},{"key":"ref_26","first-page":"415","article-title":"Therapeutic Effects of Glycyrrhizic Acid","volume":"8","author":"Ming","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1159\/000467897","article-title":"Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma","volume":"41","author":"Deng","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e001465","DOI":"10.1136\/rmdopen-2020-001465","article-title":"Long-term safety and efficacy of sirukumab for patients with rheumatoid arthritis who previously received sirukumab in randomised controlled trials (SIRROUND-LTE)","volume":"7","author":"Aletaha","year":"2021","journal-title":"RMD Open"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s40744-020-00227-2","article-title":"A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis","volume":"7","author":"Schmidt","year":"2020","journal-title":"Rheumatol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1080\/14397595.2018.1428929","article-title":"Efficacy and safety of sirukumab in Japanese patients with moderate to severe rheumatoid arthritis inadequately controlled by disease modifying anti-rheumatic drugs: Subgroup analysis of a phase 3 study","volume":"28","author":"Takeuchi","year":"2018","journal-title":"Mod. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/mabs.2.1.10328","article-title":"Canakinumab","volume":"2","author":"Dhimolea","year":"2010","journal-title":"mAbs"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Parnham, M.J. (2016). Interleukin-1 (IL-1) Inhibitors: Anakinra, Rilonacept, and Canakinumab. Compendium of Inflammatory Diseases, Springer.","DOI":"10.1007\/978-3-0348-0620-6_29-2"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1358\/dot.2009.45.6.1378935","article-title":"Rilonacept in the treatment of chronic inflammatory disorders","volume":"45","author":"McDermott","year":"2009","journal-title":"Drugs Today"},{"key":"ref_34","first-page":"3959","article-title":"IL-1 receptor antagonist anakinra enhances tumour growth inhibition in mice receiving peptide vaccination and beta-(1\u20133), (1\u20136)-D-glucan","volume":"30","author":"Harnack","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rausch, V., Sala, V., Penna, F., Porporato, P.E., and Ghigo, A. (2021). Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia. Oncogenesis, 10.","DOI":"10.1038\/s41389-020-00288-6"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Siddiqui, J.A., Pothuraju, R., Jain, M., Batra, S.K., and Nasser, M.W. (2020). Advances in cancer cachexia: Intersection between affected organs, mediators, and pharmacological interventions. Biochim. Biophys. Acta Bioenerg., 1873.","DOI":"10.1016\/j.bbcan.2020.188359"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00424-016-1933-3","article-title":"Molecular mechanism of sarcopenia and cachexia: Recent research advances","volume":"469","author":"Sakuma","year":"2017","journal-title":"Pflug. Arch."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lim, S.M., Hanif, E.A.M., and Chin, S.-F. (2021). Is targeting autophagy mechanism in cancer a good approach? The possible double-edge sword effect. Cell Biosci., 11.","DOI":"10.1186\/s13578-021-00570-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41375-020-0954-2","article-title":"Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis","volume":"35","author":"Talpaz","year":"2021","journal-title":"Leukemia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1001\/jamaoncol.2015.1590","article-title":"Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial","volume":"1","author":"Pardanani","year":"2015","journal-title":"JAMA Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4103\/2278-330X.110506","article-title":"Crizotinib: A comprehensive review","volume":"2","author":"Sahu","year":"2013","journal-title":"South Asian J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/jcph.406","article-title":"Pharmacokinetic-pharmacodynamic modeling of fostamatinib efficacy on ACR20 to support dose selection in patients with rheumatoid arthritis (RA)","volume":"55","author":"Maringwa","year":"2015","journal-title":"J. Clin. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/ajh.25125","article-title":"Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials","volume":"93","author":"Bussel","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/physrev.00027.2001","article-title":"The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction","volume":"82","author":"Glickman","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/sj.onc.1210744","article-title":"BCL-2 family regulation by the 20S proteasome inhibitor bortezomib","volume":"27","author":"Fennell","year":"2007","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1136\/annrheumdis-2014-206016","article-title":"The proteasome inhibitior bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus","volume":"74","author":"Alexander","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/RHU.0000000000000210","article-title":"Refractory Primary Sj\u00f6gren Syndrome Successfully Treated with Bortezomib","volume":"21","author":"Llorente","year":"2015","journal-title":"J. Clin. Rheumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/jcsm.12050","article-title":"Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting","volume":"7","author":"Penna","year":"2015","journal-title":"J. Cachex Sarcopenia Muscle"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.2147\/CMAR.S150653","article-title":"Carfilzomib for relapsed and refractory multiple myeloma","volume":"11","author":"Groen","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wang, Q., Li, C., Peng, X., Kang, Q., Deng, D., Zhang, L., Zheng, Y., Wang, C., Qiao, Z., and Guo, D. (2015). Combined treatment of carfilzomib and z-VAD-fmk inhibits skeletal proteolysis and apoptosis and ameliorates cancer cachexia. Med. Oncol., 32.","DOI":"10.1007\/s12032-015-0538-6"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s40265-016-0548-5","article-title":"Ixazomib: First Global Approval","volume":"76","author":"Shirley","year":"2016","journal-title":"Drugs"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1177\/1078155220963534","article-title":"A pharmacist\u2019s review of the treatment of systemic light chain amyloidosis","volume":"27","author":"Hughes","year":"2020","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/iep.12383","article-title":"Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice","volume":"102","author":"Micheletto","year":"2020","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3892\/ol.2020.12385","article-title":"Inhibition of mitochondrial and cytosolic calpain attenuates atrophy in myotubes co-cultured with colon carcinoma cells","volume":"21","author":"Zeng","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.3892\/or.2017.5396","article-title":"Calpain inhibitors ameliorate muscle wasting in a cachectic mouse model bearing CT26 colorectal adenocarcinoma","volume":"37","author":"Lin","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/S0167-4889(97)00144-4","article-title":"The calpain\u2013calpastatin system and protein degradation in fusing myoblasts","volume":"1402","author":"Barnoy","year":"1998","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of Insulin Action and Insulin Resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/S1097-2765(00)00137-4","article-title":"Molecular Basis for the Dephosphorylation of the Activation Segment of the Insulin Receptor by Protein Tyrosine Phosphatase 1B","volume":"6","author":"Salmeen","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/bjc.1997.433","article-title":"Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients","volume":"76","author":"Cariuk","year":"1997","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1096\/fj.00-0534fje","article-title":"Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-\u03ba\u0392 and STAT3","volume":"15","author":"Watchorn","year":"2001","journal-title":"FASEB J."},{"key":"ref_61","first-page":"E763","article-title":"Proteolysis-inducing factor differentially influences transcriptional regulation in endothelial subtypes","volume":"282","author":"Watchorn","year":"2002","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mantovani, G., Anker, S.D., Inui, A., Morley, J.E., Fanelli, F.R., Scevola, D., Schuster, M.W., and Yeh, S.-S. (2006). Proteolysis-Inducing Factor in Cancer Cachexia. Cachexia and Wasting: A Modern Approach, Springer.","DOI":"10.1007\/978-88-470-0552-5"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00520-002-0408-6","article-title":"The \u2018cancer cachectic factor\u2019","volume":"11","author":"Tisdale","year":"2003","journal-title":"Support. Care Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/sj.bjc.6602402","article-title":"NF-\u03baB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin\u2013proteasome system in skeletal muscle","volume":"92","author":"Wyke","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1517\/14728214.11.1.153","article-title":"Emerging Flt3 kinase inhibitors in the treatment of leukaemia","volume":"11","author":"Tickenbrock","year":"2006","journal-title":"Expert Opin. Emerg. Drugs"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Vazquez-Ortiz, G., Chisholm, C., Xu, X., Lahusen, T.J., Li, C., Sakamuru, S., Huang, R., Thomas, C.J., Xia, M., and Deng, C. (2014). Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. Breast Cancer Res., 16.","DOI":"10.1186\/bcr3682"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.bcp.2009.12.021","article-title":"Identification of known drugs that act as inhibitors of NF-\u03baB signaling and their mechanism of action","volume":"79","author":"Miller","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/blood-2009-10-246363","article-title":"Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera\/essential thrombocythemia myelofibrosis","volume":"115","author":"Santos","year":"2010","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Wylie, B., Macri, C., Mintern, J., and Waithman, J. (2019). Dendritic Cells and Cancer: From Biology to Therapeutic Intervention. Cancers, 11.","DOI":"10.3390\/cancers11040521"},{"key":"ref_70","first-page":"100","article-title":"Molecular mechanisms of parthenolide\u2019s action: Old drug with a new face","volume":"64","author":"Koprowska","year":"2010","journal-title":"Postep. Hig. Med. Dosw. (Online)"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/ddr.21565","article-title":"Dimethylaminoparthenolide reduces the incidence of dysplasia and ameliorates a wasting syndrome in HPV16-transgenic mice","volume":"80","author":"Santos","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1158\/1535-7163.MCT-17-0717","article-title":"Pharmacological Dual Inhibition of Tumor and Tumor-Induced Functional Limitations in a Transgenic Model of Breast Cancer","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/bjc.2014.271","article-title":"Molecular targets of aspirin and cancer prevention","volume":"111","author":"Alfonso","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1124\/mi.2.1.22","article-title":"Inhibition of Nuclear Factor Kappa B (NF-B): An Emerging Theme in Anti-Inflammatory Therapies","volume":"2","year":"2002","journal-title":"Mol. Interv."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0889-8553(21)00421-0","article-title":"Sulfasalazine Therapy in Inflammatory Bowel Disease","volume":"18","author":"Das","year":"1989","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI992","article-title":"Sulfasalazine: A potent and specific inhibitor of nuclear factor kappa B","volume":"101","author":"Wahl","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.2165\/00003495-200565130-00008","article-title":"Sulfasalazine","volume":"65","author":"Plosker","year":"2005","journal-title":"Drugs"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/sj.bjc.6601328","article-title":"Signal transduction pathways involved in proteolysis-inducing factor induced proteasome expression in murine myotubes","volume":"89","author":"Smith","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1038\/sj.bjc.6600236","article-title":"Development of an in-vitro model system to investigate the mechanism of muscle protein catabolism induced by proteolysis-inducing factor","volume":"86","author":"Smith","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8042","DOI":"10.1038\/srep08042","article-title":"Wnt5a promotes cancer cell invasion and proliferation by receptor-mediated endocytosis-dependent and -independent mechanisms, respectively","volume":"5","author":"Shojima","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0741-5214(95)70013-7","article-title":"Essential thrombocytosis: Underemphasized cause of large-vessel thrombosis","volume":"22","author":"Johnson","year":"1995","journal-title":"J. Vasc. Surg."},{"key":"ref_82","first-page":"119","article-title":"Drug-induced interstitial pneumonitis in essential thrombocythemia treated with anagrelide","volume":"58","author":"Kajiguchi","year":"2017","journal-title":"Rinsho Ketsueki"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/j.1476-5381.1989.tb12676.x","article-title":"Glucocorticoids inhibit prostaglandin synthesis not only at the level of phospholipase A2 but also at the level of cyclo-oxygenase\/PGE isomerase","volume":"98","author":"Wolter","year":"1989","journal-title":"Br. J. Pharmacol."},{"key":"ref_84","first-page":"782","article-title":"Low-dose hydrocortisone infusion attenuates the systemic inflammatory response syndrome","volume":"72","author":"Briegel","year":"1994","journal-title":"J. Mol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2005.01.010","article-title":"Adverse effects of topical glucocorticosteroids","volume":"54","author":"Hengge","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cellsig.2004.05.015","article-title":"Signalling pathways in the induction of proteasome expression by proteolysis-inducing factor in murine myotubes","volume":"17","author":"Wyke","year":"2005","journal-title":"Cell. Signal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1152\/physrev.00016.2008","article-title":"Mechanisms of Cancer Cachexia","volume":"89","author":"Tisdale","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1081\/CNV-120025095","article-title":"Bryostatin-1: A Novel PKC Inhibitor in Clinical Development","volume":"21","author":"Kortmansky","year":"2003","journal-title":"Cancer Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/sj.bjc.6601321","article-title":"A multicentre phase II trial of bryostatin-1 in patients with advanced renal cancer","volume":"89","author":"Madhusudan","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"596","DOI":"10.2174\/092986713804999303","article-title":"Treatment of Estrogen Receptor-Positive Breast Cancer","volume":"20","author":"Lumachi","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_91","first-page":"2462","article-title":"Inhibition of protein kinase C by tamoxifen","volume":"45","author":"Liskamp","year":"1985","journal-title":"Cancer Res."},{"key":"ref_92","first-page":"855","article-title":"Tamoxifen treatment and gynecologic side effects: A review","volume":"97","author":"Mourits","year":"2001","journal-title":"Obstet. Gynecol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.tem.2012.10.006","article-title":"Cancer cachexia: Malignant inflammation, tumorkines, and metabolic mayhem","volume":"24","author":"Tsoli","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1177\/1535370216683282","article-title":"The role of adipose tissue in cancer-associated cachexia","volume":"242","author":"Vaitkus","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.apsb.2019.10.006","article-title":"Monoacylglycerol lipase inhibitors: Modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders","volume":"10","author":"Deng","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9062","DOI":"10.1021\/acs.jmedchem.8b00951","article-title":"Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders","volume":"61","author":"Cisar","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9059","DOI":"10.1021\/acs.jmedchem.8b01405","article-title":"Activity-Based Protein Profiling Delivers Selective Drug Candidate ABX-1431, a Monoacylglycerol Lipase Inhibitor, To Control Lipid Metabolism in Neurological Disorders","volume":"61","author":"Jiang","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Mannelli, M., Gamberi, T., Magherini, F., and Fiaschi, T. (2020). The Adipokines in Cancer Cachexia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144860"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.molmed.2013.02.006","article-title":"The role of triglyceride lipases in cancer associated cachexia","volume":"19","author":"Das","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7153","DOI":"10.1074\/jbc.M109.053942","article-title":"Chronic Peroxisome Proliferator-activated Receptor \u03b3 (PPAR\u03b3) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes","volume":"285","author":"Petrovic","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1002\/jcb.26631","article-title":"PPAR\u03b3 activation mitigates glucocorticoid receptor-induced excessive lipolysis in adipocytes via homeostatic crosstalk","volume":"119","author":"Hasan","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"You, W., Xu, Z., Sun, Y., Valencak, T.G., Wang, Y., and Shan, T. (2020). GADD45\u03b1 drives brown adipose tissue formation through upregulating PPAR\u03b3 in mice. Cell Death Dis., 11.","DOI":"10.1038\/s41419-020-02802-5"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Colson, C., Batrow, P.-L., Gautier, N., Rochet, N., Ailhaud, G., Peiretti, F., and Amri, E.-Z. (2020). The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes. Cells, 9.","DOI":"10.3390\/cells9112433"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ejmech.2018.03.032","article-title":"Design and synthesis of aryloxypropanolamine as \u03b23-adrenergic receptor antagonist in cancer and lipolysis","volume":"150","author":"Jin","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Tabuchi, C., and Sul, H.S. (2021). Signaling Pathways Regulating Thermogenesis. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.595020"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Frishman, W.H. (1988). Beta-adrenergic receptor blockers. Adverse effects and drug interactions. Hypertension, 11.","DOI":"10.1161\/01.HYP.11.3_Pt_2.II21"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Canov\u00e1, N., Lincov\u00e1, D., and Farghali, H. (2004). Inconsistent role of nitric oxide on lipolysis in isolated rat adipocytes. Physiol. Res., 54.","DOI":"10.33549\/physiolres.930678"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.niox.2005.06.006","article-title":"Nitric oxide production from rat adipocytes is modulated by \u03b23-adrenergic receptor agonists and is involved in a cyclic AMP-dependent lipolysis in adipocytes","volume":"14","author":"Farghali","year":"2006","journal-title":"Nitric Oxide"},{"key":"ref_109","first-page":"139","article-title":"Betablocking drugs in essential hypertension: Transdermal bupranolol compared with oral metoprolol","volume":"12","author":"Jeck","year":"1992","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.exer.2007.01.010","article-title":"Vasodilatory mechanism of levobunolol on vascular smooth muscle cells","volume":"84","author":"Dong","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_111","first-page":"1741","article-title":"Bradyarrhythmias secondary to topical levobunolol hydrochloride solution","volume":"9","author":"Lin","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1046\/j.1365-2362.2001.00872.x","article-title":"Cardiovascular effects of beta 3-adrenoceptor stimulation in perinephritic hypertension","volume":"31","author":"Donckier","year":"2001","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"110688","DOI":"10.1016\/j.ijporl.2021.110688","article-title":"Propranolol versus nadolol for treatment of pediatric subglottic hemangioma","volume":"144","author":"Yang","year":"2021","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Jia, Y., and Leung, S.-W. (2014). Drug efficacy in treating stable angina pectoris: A protocol for network meta-analysis of randomised controlled trials. BMJ Open, 4.","DOI":"10.1136\/bmjopen-2014-005453"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e20191035","DOI":"10.1542\/peds.2019-1035","article-title":"Death Associated with Nadolol for Infantile Hemangioma: A Case for Improving Safety","volume":"145","author":"McGillis","year":"2019","journal-title":"Pediatrics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000443373","article-title":"Adjuvant Treatment of Graves\u2019 Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations","volume":"5","author":"Lantz","year":"2016","journal-title":"Eur. Thyroid. J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1023\/A:1020563913045","article-title":"New Insights into the Biology of the Acute Phase Response","volume":"19","author":"Suffredini","year":"1999","journal-title":"J. Clin. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1631\/jzus.2005.B1045","article-title":"Acute phase reaction and acute phase proteins","volume":"6","author":"Gruys","year":"2005","journal-title":"J. Zhejiang Univ. A"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/SPC.0b013e3283186be2","article-title":"Cachexia, survival and the acute phase response","volume":"2","author":"Stephens","year":"2008","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_120","first-page":"E707","article-title":"Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients","volume":"279","author":"Barber","year":"2000","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/(SICI)1096-9896(199703)181:3<257::AID-PATH756>3.0.CO;2-U","article-title":"Cytokines and the hepatic acute phase response","volume":"181","author":"Moshage","year":"1997","journal-title":"J. Pathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12031-018-1202-3","article-title":"An Intraperitoneal Treatment with Calcitonin Gene-Related Peptide (CGRP) Regulates Appetite, Energy Intake\/Expenditure, and Metabolism","volume":"67","author":"Sanford","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/jcsm.12028","article-title":"One-year intranasal application of growth hormone releasing peptide-2 improves body weight and hypoglycemia in a severely emaciated anorexia nervosa patient","volume":"6","author":"Haruta","year":"2015","journal-title":"J. Cachex Sarcopenia Muscle"},{"key":"ref_124","first-page":"E486","article-title":"Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats","volume":"288","author":"Granado","year":"2005","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"H1643","DOI":"10.1152\/ajpheart.01042.2004","article-title":"GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure","volume":"289","author":"Xu","year":"2005","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_126","first-page":"857","article-title":"Pharmacological Characteristics of KP-102 (GHRP-2), a Potent Growth Hormone-Releasing Peptide","volume":"54","author":"Doi","year":"2004","journal-title":"Arzneimittelforschung"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"101321","DOI":"10.1016\/j.ghir.2020.101321","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of macimorelin in healthy adults: Results of a single-dose, randomized controlled study","volume":"52","author":"Klaus","year":"2020","journal-title":"Growth Horm. IGF Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/ndt\/gfw474","article-title":"Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: A randomized blinded study","volume":"33","author":"Campbell","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_129","first-page":"435","article-title":"Ghrelin Agonist JMV 1843 Increases Food Intake, Body Weight and Expression of Orexigenic Neuropeptides in Mice","volume":"62","author":"Demianova","year":"2013","journal-title":"Physiol. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"601","DOI":"10.7326\/0003-4819-149-9-200811040-00003","article-title":"Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults","volume":"149","author":"Nass","year":"2008","journal-title":"Ann. Intern. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1177\/0091270007310380","article-title":"Ghrelin Agonist (TZP-101): Safety, Pharmacokinetics and Pharmacodynamic Evaluation in Healthy Volunteers: A Phase I, First-in-Human Study","volume":"48","author":"Lasseter","year":"2008","journal-title":"J. Clin. Pharmacol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.mce.2011.02.010","article-title":"The ghrelin axis in disease: Potential therapeutic indications","volume":"340","author":"Nass","year":"2011","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"69219","DOI":"10.18632\/oncotarget.18215","article-title":"Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL and Burkitt\u2019s lymphoma anti-tumor activity","volume":"8","author":"Curtis","year":"2017","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Braga, M., Kaliszczak, M., Carroll, L., Schug, Z.T., Heinzmann, K., Baxan, N., Benito, A., Valbuena, G.N., Stribbling, S., and Beckley, A. (2020). Tracing Nutrient Flux Following Monocarboxylate Transporter-1 Inhibition with AZD3965. Cancers, 12.","DOI":"10.3390\/cancers12061703"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3324\/haematol.2016.163030","article-title":"Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma","volume":"102","author":"Noble","year":"2017","journal-title":"Haematologica"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Halford, S.E.R., Jones, P., Wedge, S., Hirschberg, S., Katugampola, S., Veal, G., Payne, G., Bacon, C., Potter, S., and Griffin, M. (2017). A first-in-human first-in-class (FIC) trial of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in patients with advanced solid tumours. J. Clin. Oncol., 35.","DOI":"10.1200\/JCO.2017.35.15_suppl.2516"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/nn.4574","article-title":"Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus","volume":"20","author":"Campos","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.3389\/fphar.2019.01577","article-title":"Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine: Evidence from Randomized Controlled Trials","volume":"10","author":"Gao","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e24741","DOI":"10.1097\/MD.0000000000024741","article-title":"Calcitonin gene-related peptide receptor antagonist ubrogepant for the treatment of acute migraine","volume":"100","author":"Zhang","year":"2021","journal-title":"Medicine"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/cpdd.916","article-title":"Single-Dose Pharmacokinetics and Safety of Atogepant in Adults with Hepatic Impairment: Results from an Open-Label, Phase 1 Trial","volume":"10","author":"Boinpally","year":"2021","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/WCO.0000000000000806","article-title":"Gepants, calcitonin-gene-related peptide receptor antagonists: What could be their role in migraine treatment?","volume":"33","author":"Ajona","year":"2020","journal-title":"Curr. Opin. Neurol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.physbeh.2010.03.011","article-title":"Hypothalamic mechanisms in cachexia","volume":"100","author":"Grossberg","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.nut.2009.07.003","article-title":"Update on melanocortin interventions for cachexia: Progress toward clinical application","volume":"26","author":"DeBoer","year":"2010","journal-title":"Nutrition"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/35007534","article-title":"Central nervous system control of food intake","volume":"404","author":"Schwartz","year":"2000","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1615\/CritRevOncog.v17.i3.20","article-title":"Neuroinflammation: A contributing factor to the pathogenesis of cancer cachexia","volume":"17","author":"Laviano","year":"2012","journal-title":"Crit. Rev. Oncog."},{"key":"ref_146","first-page":"1432","article-title":"Role of the central melanocortin system in cachexia","volume":"61","author":"Marks","year":"2001","journal-title":"Cancer Res."},{"key":"ref_147","first-page":"E1000","article-title":"Neural control of the anorexia-cachexia syndrome","volume":"295","author":"Laviano","year":"2008","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.cmet.2007.09.012","article-title":"Serotonin and the Orchestration of Energy Balance","volume":"6","author":"Tecott","year":"2007","journal-title":"Cell Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/BF01245044","article-title":"Plasma and CSF tryptophan in cancer anorexia","volume":"81","author":"Cangiano","year":"1990","journal-title":"J. Neural Transm."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.neuron.2006.06.004","article-title":"Serotonin Reciprocally Regulates Melanocortin Neurons to Modulate Food Intake","volume":"51","author":"Heisler","year":"2006","journal-title":"Neuron"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1007\/BF01642906","article-title":"5-HT2 receptor antagonists and migraine therapy","volume":"238","author":"Mylecharane","year":"1991","journal-title":"J. Neurol."},{"key":"ref_152","unstructured":"Aronson, J.K. (2016). Pizotifen. Meyler\u2019s Side Effects of Drugs, Elsevier. [16th ed.]."},{"key":"ref_153","first-page":"983","article-title":"Trazodone is a potent agonist at 5-HT2C receptors mediating inhibition of the N-methyl-D-aspartate\/nitric oxide\/cyclic GMP pathway in rat cerebellum","volume":"285","author":"Marcoli","year":"1998","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.2174\/1381612821666150619092236","article-title":"Off-Label Trazodone Prescription: Evidence, Benefits and Risks","volume":"21","author":"Bossini","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1517\/14656566.2012.699523","article-title":"Off-label uses of trazodone: A review","volume":"13","author":"Bossini","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_156","first-page":"6","article-title":"The psychopharmacology of ziprasidone: Receptor-binding properties and real-world psychiatric practice","volume":"64","author":"Stahl","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_157","first-page":"226","article-title":"Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors","volume":"295","author":"Grinde","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/bs.apha.2017.09.009","article-title":"Unique Effects of Clozapine: A Pharmacological Perspective","volume":"82","author":"Khokhar","year":"2018","journal-title":"Adv. Pharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s00213-009-1639-8","article-title":"Olanzapine-induced weight gain in the rat: Role of 5-HT2C and histamine H1 receptors","volume":"207","author":"Kirk","year":"2009","journal-title":"Psychopharmacology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"18224","DOI":"10.18632\/oncotarget.24804","article-title":"Increased gut permeability in cancer cachexia: Mechanisms and clinical relevance","volume":"9","author":"Bindels","year":"2018","journal-title":"Oncotarget"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1097\/SPC.0000000000000017","article-title":"Gut barrier dysfunction and microbial translocation in cancer cachexia","volume":"7","author":"Klein","year":"2013","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.3748\/wjg.v19.i26.4137","article-title":"Effects of rhein on intestinal epithelial tight junction in IgA nephropathy","volume":"19","author":"Peng","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1038\/ctg.2016.54","article-title":"Human Intestinal Barrier Function in Health and Disease","volume":"7","author":"Wells","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1749-6632.2012.06538.x","article-title":"Zonulin, regulation of tight junctions, and autoimmune diseases","volume":"1258","author":"Fasano","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Enomoto, H., Yeatts, J., Carbajal, L., Krishnan, B.R., Madan, J.P., Laumas, S., Blikslager, A.T., and Messenger, K.M. (2021). In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249179"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"5788","DOI":"10.2174\/0929867328666210104110053","article-title":"The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases","volume":"28","author":"Troisi","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1038\/ajg.2012.211","article-title":"A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge","volume":"107","author":"Leffler","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/1753-0407.12986","article-title":"Faecalibacterium prausnitzii\u2014derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression","volume":"12","author":"Xu","year":"2019","journal-title":"J. Diabetes"},{"key":"ref_169","first-page":"G970","article-title":"Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-\u03b1 on tight junction proteins and signaling pathways in intestinal epithelial cells","volume":"304","author":"Fischer","year":"2013","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40266-016-0347-4","article-title":"Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO","volume":"33","author":"Pavelka","year":"2016","journal-title":"Drugs Aging"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1007\/s10067-019-04587-1","article-title":"Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response to methotrexate: A pilot randomized, double-blind, placebo-controlled add-on trial","volume":"38","author":"Louthrenoo","year":"2019","journal-title":"Clin. Rheumatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"840","DOI":"10.2174\/0929867327666200728134755","article-title":"Effects of Diacerein Intake on Cardiometabolic Profiles in Type 2 Diabetics: A Systematic Review and Meta-Analysis of Clinical Trials","volume":"28","author":"Tabrizi","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.intimp.2019.03.030","article-title":"Rhein protects against barrier disruption and inhibits inflammation in intestinal epithelial cells","volume":"71","author":"Zhuang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000503054","article-title":"Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function","volume":"105","author":"Nishii","year":"2019","journal-title":"Pharmacology"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000508864","article-title":"Risk Factors for Adverse Events in Patients with Chronic Constipation Following Lubiprostone Administration","volume":"39","author":"Eguchi","year":"2020","journal-title":"Dig. Dis."},{"key":"ref_176","first-page":"1087","article-title":"Drug databases and their contributions to drug repurposing","volume":"112","author":"Omidi","year":"2019","journal-title":"Genomics"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"D1098","DOI":"10.1093\/nar\/gkt1143","article-title":"The IUPHAR\/BPS Guide to pharmacology: An expert-driven knowledgebase of drug targets and their ligands","volume":"42","author":"Pawson","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_178","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":"ref_179","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1093\/bib\/bbaa003","article-title":"Exploration of databases and methods supporting drug repurposing: A comprehensive survey","volume":"22","author":"Tanoli","year":"2020","journal-title":"Brief. Bioinform."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Schirrmacher, V. (2020). Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110526"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"e15016","DOI":"10.14814\/phy2.15016","article-title":"Voluntary exercise prevents abnormal muscle mitochondrial morphology in cancer cachexia mice","volume":"9","author":"Kitaoka","year":"2021","journal-title":"Physiol. Rep."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.bbalip.2014.03.004","article-title":"Molecular insights into mitochondrial dysfunction in cancer-related muscle wasting","volume":"1841","author":"Antunes","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s13539-012-0071-9","article-title":"Cancer cachexia is associated with a decrease in skeletal muscle mitochondrial oxidative capacities without alteration of ATP production efficiency","volume":"3","author":"Julienne","year":"2012","journal-title":"J. Cachex Sarcopenia Muscle"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s13539-014-0154-x","article-title":"Cachexia: A problem of energetic inefficiency","volume":"5","author":"Argiles","year":"2014","journal-title":"J. Cachex Sarcopenia Muscle"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Vanderveen, B.N., Fix, D.K., and Carson, J.A. (2017). Disrupted Skeletal Muscle Mitochondrial Dynamics, Mitophagy, and Biogenesis during Cancer Cachexia: A Role for Inflammation. Oxidative Med. Cell. Longev., 2017.","DOI":"10.1155\/2017\/3292087"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-pharmtox-010919-023537","article-title":"Using What We Already Have: Uncovering New Drug Repurposing Strategies in Existing Omics Data","volume":"60","author":"Pulley","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/11\/1084\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:12Z","timestamp":1760167452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/11\/1084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,26]]},"references-count":186,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ph14111084"],"URL":"https:\/\/doi.org\/10.3390\/ph14111084","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,26]]}}}