{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T14:34:41Z","timestamp":1781879681358,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Foundation of China","doi-asserted-by":"publisher","award":["81773755"],"award-info":[{"award-number":["81773755"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The plant-derived toxin ricin is classified as a type 2 ribosome-inactivating protein (RIP) and currently lacks effective clinical antidotes. The toxicity of ricin is mainly due to its ricin toxin A chain (RTA), which has become an important target for drug development. Previous studies have identified two essential binding pockets in the active site of RTA, but most existing inhibitors only target one of these pockets. In this study, we used computer-aided virtual screening to identify a compound called RSMI-29, which potentially interacts with both active pockets of RTA. We found that RSMI-29 can directly bind to RTA and effectively attenuate protein synthesis inhibition and rRNA depurination induced by RTA or ricin, thereby inhibiting their cytotoxic effects on cells in vitro. Moreover, RSMI-29 significantly reduced ricin-mediated damage to the liver, spleen, intestine, and lungs in mice, demonstrating its detoxification effect against ricin in vivo. RSMI-29 also exhibited excellent drug-like properties, featuring a typical structural moiety of known sulfonamides and barbiturates. These findings suggest that RSMI-29 is a novel small-molecule inhibitor that specifically targets ricin toxin A chain, providing a potential therapeutic option for ricin intoxication.<\/jats:p>","DOI":"10.3390\/molecules29071435","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T12:28:06Z","timestamp":1711369686000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification and Biological Evaluation of a Novel Small-Molecule Inhibitor of Ricin Toxin"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5195-9379","authenticated-orcid":false,"given":"Xinran","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China"},{"name":"Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aili","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Operational Medicine, Institute of Environmental and Operational Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Tianjin 300050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sowa-Rogozi\u0144ska, N., Sominka, H., Nowakowska-Go\u0142acka, J., Sandvig, K., and S\u0142omi\u0144ska Wojew\u00f3dzka, M. 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