150787 20251017144651.0 doi 10.1038/s41598-025-87535-1 sideral 142858 ART-2025-142858 eng Weinhäupl, Katharina Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development 2025 Access copy available to the general public Unrestricted MtbClpC1 is a promising drug target against tuberculosis. Recent studies have shown that several natural product antibiotics targeting the unfoldase N-terminal domain can impair MtbClpC1 function resulting in cell death. While the pharmacological properties of these natural product antibiotics prevent their use in the clinic, similar molecules binding to the same binding pockets can result in new drugs against Mtb. Here we demonstrate that we successfully used in silico screening to identify new ClpC1 N-terminal domain binders with micromolar affinity from a small compound library. In addition, we experimentally demonstrate that the new compounds bind to the same pockets used by the natural product antibiotics and inhibit ClpC1 function. info:eu-repo/grantAgreement/ES/ISCIII/PI21-00394 info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Meuret, Louis Desrat, Sandy Roussy, Fanny Morellet, Nelly Beaupierre, Sandra Guillou, Catherine van Heijenoort, Carine Abian, Olga Universidad de Zaragoza (orcid)0000-0001-5664-1729 Vega, Sonia (orcid)0000-0002-1232-6310 Wolf, Ian Akopian, Tatos Krandor, Olga Rubin, Eric Velazquez-Campoy, Adrian Universidad de Zaragoza (orcid)0000-0001-5702-4538 Gauto, Diego Fraga, Hugo 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 15, 1 (2025), 4146 [14 pp.] Sci. rep. (Nat. Publ. Group) Scientific reports (Nature Publishing Group) 2045-2322 5779353 http://zaguan.unizar.es/record/150787/files/texto_completo.pdf Versión publicada 2657076 http://zaguan.unizar.es/record/150787/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:150787 articulos driver 2025-10-17-14:36:35 ARTICLE