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Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti\u2010fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS\u201001, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS\u201001 could time\u2010 and dose\u2010dependently prolong mice forced\u2010swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS\u201001 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In <jats:italic>Orm<\/jats:italic>\u2010deficient mice, the anti\u2010fatigue and glycogen\u2010elevation activity of HMS\u201001 disappeared. Therefore, HMS\u201001 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.<\/jats:p>","DOI":"10.1111\/1440-1681.13873","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:05:06Z","timestamp":1717113906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A non\u2010antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti\u2010fatigue protein orosomucoid in mice"],"prefix":"10.1111","volume":"51","author":[{"given":"Jiayi","family":"Feng","sequence":"first","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengyue","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingyan","family":"Sun","sequence":"additional","affiliation":[{"name":"China Institute of Pharmaceutical Industry  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"},{"name":"Key Lab of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-9718","authenticated-orcid":false,"given":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.194"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111587"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.5620\/eht.2012.27.e2012007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","unstructured":"Kang D Hong H Kim K et al. 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