{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:28:24Z","timestamp":1782289704508,"version":"3.54.5"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tianjin Key R&D Program","award":["19YFZCSY00350"],"award-info":[{"award-number":["19YFZCSY00350"]}]},{"name":"Tianjin Key R&D Program","award":["17ZXXYSY00090"],"award-info":[{"award-number":["17ZXXYSY00090"]}]},{"name":"Tianjin Major Scientific and Technological Projects of New Drug Creation","award":["19YFZCSY00350"],"award-info":[{"award-number":["19YFZCSY00350"]}]},{"name":"Tianjin Major Scientific and Technological Projects of New Drug Creation","award":["17ZXXYSY00090"],"award-info":[{"award-number":["17ZXXYSY00090"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Amifostine is a radioprotector with high efficacy but poor safety, short half\u2010life, no oral formulation, and poor compliance, which limits its application. With the increasing risk of exposure to radiation, the development of new radioprotective agents is critical. We previously synthesized a new amifostine derivative, the small molecule compound HL\u2010003. In this study, we focused on evaluating the radioprotective properties of HL\u2010003. Using the <jats:italic>in vitro<\/jats:italic> 2,2\u2010diphenyl\u20101\u2010picrylhydrazyl assay, we initially confirmed HL\u2010003 as a strong antioxidant and demonstrated that its free radical scavenging activity was stronger than that of amifostine. Then, we performed an acute toxicity test, a 28\u2010day toxicity test, a 30\u2010day survival rate test, and a pharmacokinetic study, all of which provided aggregate evidence that HL\u2010003 functioned as a small molecule radioprotector with high efficacy, a favorable safety profile, a long half\u2010life, and oral administration. The intestinal radioprotective mechanism of HL\u2010003 was explored in male C57 mice after abdominal irradiation by analyzing intestinal tissue samples with hematoxylin\u2010eosin staining, immunohistochemistry, TUNEL staining, and immunofluorescence detection. The results showed that HL\u2010003 protected intestinal DNA from radiation damage and suppressed the expression of phosphorylated histone H2AX, phosphorylated p53, and the apoptosis\u2010related proteins caspase\u20108 and caspase\u20109, which contributed to maintaining the normal morphology of the small intestine and provided insights into the mechanism of radioprotection. Thus, HL\u2010003 is a small molecule radioprotector with a potential application in radiation medicine.<\/jats:p>","DOI":"10.1155\/2021\/6683836","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T03:20:15Z","timestamp":1613877615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preclinical Evaluation of Safety, Pharmacokinetics, Efficacy, and Mechanism of Radioprotective Agent HL\u2010003"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-2234","authenticated-orcid":false,"given":"Yahong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7014-8762","authenticated-orcid":false,"given":"Longfei","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8846-9855","authenticated-orcid":false,"given":"Yuying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-9097","authenticated-orcid":false,"given":"Hongqi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0000000000000279"},{"key":"e_1_2_10_2_2","volume-title":"\u201cRadiobiology for the Radiobiologist\u201d 6th edition","author":"Hall E. 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