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There is a real medical need for a specific copper chelator to regulate the copper excess efficiently, at lower doses than those used for penicillamine (DPA) or trientine (TETA), and with lower toxicity in long-term treatments. Methods: The efficiency of the specific Cu(II) chelator named TDMQ20 was evaluated by oral treatment of TX mice, used as a WD model, and compared with those of DPA, TETA, and also tetrathiomolybdate (bcTTM). We documented TDMQ20\u2032s ability to (i) decrease the hepatic copper load, (ii) increase the amount and ferroxidase activity of ceruloplasmin (CP), and (iii) regulate liver proteins that are impaired in WD mice. Results: Compared to the other copper chelators, TDMQ20 was the only one that efficiently mediated excretion of Cu and restoration of active ceruloplasmin levels at doses 8 times lower than DPA. Such efficacy is related to the design of this chelator, which specifically coordinates Cu(II) as a discrete and soluble complex. Conversely, DPA, TETA, and bcTTM give rise to various complexes with copper ions, often with oligomeric or cluster structures that can be retained in blood circulation or sequestered by proteins. Conclusions: Taking into consideration all the advantages of TDMQ20 compared to other ligands, including its lack of toxicity during long-term administration in mice, the drug candidate TDMQ20 appears to be a first-class challenger to the currently used treatments, i.e., DPA, TETA, and bcTTM.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091237","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:08:17Z","timestamp":1758560897000},"page":"1237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TDMQ20 as A Drug Candidate for Wilson\u2019s Disease: Comparison with D-Penicillamine, Trientine, and Tetrathiomolybdate In Vitro and In Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Yingshan","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiling","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangwei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6496-0495","authenticated-orcid":false,"given":"Michel","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS, Inserm ERL 1289, 205 route de Narbonne, 31077 Toulouse, Cedex 4, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-6776","authenticated-orcid":false,"given":"Anne","family":"Robert","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie de Coordination du CNRS, Inserm ERL 1289, 205 route de Narbonne, 31077 Toulouse, Cedex 4, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2200-7142","authenticated-orcid":false,"given":"Bernard","family":"Meunier","sequence":"additional","affiliation":[{"name":"School of Chemical Engineering and Light Industry, Guangdong University of Technology (GDUT), Higher Education Mega Center, Guangzhou 510006, China"},{"name":"Laboratoire de Chimie de Coordination du CNRS, Inserm ERL 1289, 205 route de Narbonne, 31077 Toulouse, Cedex 4, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(07)60196-2","article-title":"Wilson\u2019s disease","volume":"369","author":"Ala","year":"2007","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1474-4422(14)70190-5","article-title":"Wilson\u2019s disease and other neurological copper disorders","volume":"14","author":"Bandmann","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"634","DOI":"10.4254\/wjh.v13.i6.634","article-title":"Wilson\u2019s disease: Revisiting an old friend","volume":"13","author":"Ampuero","year":"2021","journal-title":"World J. 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