{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:09:38Z","timestamp":1792660178747,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T00:00:00Z","timestamp":1412035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Anamorelin HCl (ANAM) is a novel, orally active, ghrelin receptor agonist in clinical development for the treatment of cancer cachexia. We report in vitro and in vivo studies evaluating the preclinical pharmacologic profile of ANAM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fluorescent imaging plate reader and binding assays in HEK293 and baby hamster kidney cells determined the agonist and antagonist activity of ANAM, and its affinity for the ghrelin receptor. Rat pituitary cells were incubated with ANAM to evaluate its effect on growth hormone (GH) release. In vivo, rats were treated with ANAM 3, 10, or 30\u00a0mg\/kg, or control orally, once daily for 6\u00a0days to evaluate the effect on food intake (FI) and body weight (BW), and once to assess GH response. In pigs, single (3.5\u00a0mg\/kg) or continuous (1\u00a0mg\/kg\/day) ANAM doses were administered to assess GH and insulin\u2010like growth factor (IGF\u20101) response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ANAM showed significant agonist and binding activity on the ghrelin receptor, and stimulated GH release in vitro. In rats, ANAM significantly and dose\u2010dependently increased FI and BW at all dose levels compared with control, and significantly increased GH levels at 10 or 30\u00a0mg\/kg doses. Increases in GH and IGF\u20101 levels were observed following ANAM administration in pigs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ANAM is a potent and highly specific ghrelin receptor agonist with significant appetite\u2010enhancing activity, leading to increases in FI and BW, and a stimulatory effect on GH secretion. These results support the continued investigation of ANAM as a potential treatment of cancer anorexia\u2010cachexia syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s13539-014-0159-5","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T15:55:08Z","timestamp":1412006108000},"page":"329-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Anamorelin HCl (ONO\u20107643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia\u2010cachexia syndrome: preclinical profile"],"prefix":"10.1002","volume":"5","author":[{"given":"Claudio","family":"Pietra","sequence":"first","affiliation":[{"name":"Helsinn Healthcare SA, Research and Preclinical Department  6915 Lugano"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Takeda","sequence":"additional","affiliation":[{"name":"ONO Pharmaceutical Co., Ltd, Discovery Research Laboratories  Osaka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Tazawa-Ogata","sequence":"additional","affiliation":[{"name":"ONO Pharmaceutical Co., Ltd, Discovery Research Laboratories  Osaka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Minami","sequence":"additional","affiliation":[{"name":"ONO Pharmaceutical Co., Ltd, Discovery Research Laboratories  Osaka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yuanfeng","sequence":"additional","affiliation":[{"name":"HD Biosciences  Shanghai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth Manning","family":"Duus","sequence":"additional","affiliation":[{"name":"Helsinn Therapeutics Inc.  Bridgewater NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Northrup","sequence":"additional","affiliation":[{"name":"Helsinn Therapeutics Inc.  Bridgewater NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/601434"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(05)80001-3"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-010-0127-z"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)10090-9"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601781"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyt075"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-061509-131248"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2008"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/45230"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2013.727390"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-410473-0.00003-9"},{"key":"e_1_2_6_14_1","first-page":"1393","article-title":"Effects of ghrelin on anorexia in tumor\u2010bearing mice with eicosanoid\u2010related cachexia","volume":"28","author":"Wang W","year":"2006","journal-title":"Int J Oncol"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0016"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031768"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27430"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24917"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2011.01.021"},{"key":"e_1_2_6_20_1","unstructured":"Kumor K Polvino W. Biologic activity of RC\u20101291 a novel oral ghrelin mimetic for cancer anorexia\/cachexia: results from a Phase I randomized double\u2010blind placebo\u2010controlled trial in healthy volunteers. Support Care Cancer. 2006;14:593. Abstract 03\u2013009."},{"key":"e_1_2_6_21_1","unstructured":"Blum R Polvino W. Pharmacokinetic (PK) profile of RC\u20101291 a novel oral ghrelin mimetic for the treatment of cancer anorexia\/cachexia. Support Care Cancer. 2006;14:593. Abstract 03\u2013010."},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-5-594"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-012-1500-1"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","unstructured":"Abernethy AP Temel JS Currow D Gleich LL Friend J. Phase III clinical trials with anamorelin HCl a novel oral treatment for NSCLC cachexia. J Clin Oncol. 2013;31(suppl): Abstract TPS9649.","DOI":"10.1200\/jco.2013.31.15_suppl.tps9649"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-013-1800-0"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ghir.2008.12.003"},{"key":"e_1_2_6_27_1","unstructured":"Temel J Bondarde S Jain M Allen S Mann W. Efficacy and safety of anamorelin HCl in NSCLC patients: results from a randomized double\u2010blind placebo-controlled multicentre phase II study. Eur J Cancer. 2013;49 (Suppl 2): Abstract 1308."},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0632"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-149-9-200811040-00003"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.41.7"},{"key":"e_1_2_6_31_1","first-page":"165","volume-title":"William's textbook of endocrinology","author":"Reichlin S","year":"1998"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2160"},{"key":"e_1_2_6_33_1","unstructured":"Ali SA Garcia JM. Randomized clinical trial of the novel oral ghrelin mimetic macimorelin in the treatment of cancer cachexia: study design and preliminary results. Endocr Rev. 2013;34: Abstract MON\u2010327."},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0027"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.153"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007273"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4195"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00175-8"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700767"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.6303"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm059"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1007%2Fs13539-014-0159-5","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s13539-014-0159-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T02:01:02Z","timestamp":1700618462000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s13539-014-0159-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,30]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["10.1007\/s13539-014-0159-5"],"URL":"https:\/\/doi.org\/10.1007\/s13539-014-0159-5","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,30]]},"assertion":[{"value":"2014-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}