{ "abstract": "Celastrol, a quinone methide pentacyclic triterpenoid obtained mainly from the roots of Tripterygium wilfordii Hook. f., forms covalent, often reversible, adducts with cysteine thiols in regulatory proteins, which underlies its multi-targeted action. This review summarises the preclinical evidence on celastrol and its derivatives in breast, ovarian, and cervical cancer and the nanocarriers designed to overcome its pharmacological limitations. Chemoproteomics has defined covalent targets at three distinguishable levels of evidence: residue-mapped and confirmed by mutagenesis or by genetic validation for IKKβ, PRDX1, PKM2, HMGB1, and COMMD3; binding measured without mapping of the residue for the Hsp90–Cdc37 complex, the proteasome, further peroxiredoxins, and mitochondrial isocitrate dehydrogenases; and inferred from functional or degradation readouts for the remainder. Almost all of this work was performed outside the three tumour types, so the target catalogue applies to them by extrapolation. Across in vitro and in vivo models it induces cell-cycle arrest, apoptosis, and oxidative and mitochondrial stress, modulates NF-κB, PI3K/Akt/mTOR, JAK/STAT3, MAPK, Wnt/β-catenin, and Hippo signalling, and limits migration, invasion, and angiogenesis. It also engages paraptosis, endoplasmic reticulum stress, pyroptosis, ferroptosis, cuproptosis, and immunogenic cell death, and remodels the tumour immune microenvironment. Modification at the C-20 carboxyl group and the A/B ring system, including proteolysis-targeting chimeras, has improved potency and selectivity. Because solubility, oral bioavailability, and the therapeutic window remain limiting, liposomal, micellar, carrier-free, and biomimetic nanocarriers have been developed to improve tumour selectivity and safety. Translation will depend on optimised derivatives, advanced delivery, sustainable production, rigorous pharmacokinetic and toxicological evaluation, and the pharmacoeconomic considerations examined here.", "abstract_shown": true, "affiliations": [ "Department of Economic and Medical Informatics, University of Lodz, 90-214 Lodz, Poland", "Students Research Group, Department of Medical Biology, Medical University of Lodz, 90-151 Lodz, Poland", "Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland", "Students Research Club NANO, Department of Chemistry, Lodz University of Technology, Stefanowskiego 16, 90-537 Lodz, Poland", "Department of Surgical Oncology, Medical University of Lodz, 251 Pomorska St., 93-513 Lodz, Poland", "Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jagiellońska 13-15, 85-067 Bydgoszcz, Poland", "Eurecat, Centre Tecnològic de Catalunya, C/Marcel·lí Domingo 2, 43007 Tarragona, Spain", "Littoral Environnement et Sociétés UMRi CNRS 7266 LIENSs, La Rochelle Université, 17042 La Rochelle, France", "Chemistry Interdisciplinary Project (ChIP) Research Center, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy", "Department of Medical Biology, Medical University of Lodz, Muszyńskiego 1, 90-151 Lodz, Poland" ], "article_type": "review article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Anna Merecz-Sadowska", "orcid": "0000-0001-9987-4573" }, { "affs": [ 1 ], "name": "Maciej Kowalski", "orcid": "0009-0000-8167-7010" }, { "affs": [ 2 ], "name": "Tomasz Kowalczyk", "orcid": "0000-0002-4559-5015" }, { "affs": [ 3 ], "name": "Maksymilian Trzciński", "orcid": "0009-0006-7775-6940" }, { "affs": [ 1 ], "name": "Martyna Muskała", "orcid": "0009-0001-8896-9320" }, { "affs": [ 4 ], "name": "Janusz Piekarski" }, { "affs": [ 5, 6 ], "name": "Bartosz Tylkowski", "orcid": "0000-0002-4163-0178" }, { "affs": [ 7 ], "name": "Laurent Picot", "orcid": "0000-0003-4656-3557" }, { "affs": [ 8 ], "name": "Filippo Maggi", "orcid": "0000-0003-1375-4744" }, { "affs": [ 9 ], "name": "Przemysław Sitarek", "orcid": "0000-0001-5495-3550" } ], "bibtex": "https://research.draconitic.com/paper/0h68c7xy5zd67.bib", "cited_by": 0, "doi": "10.3390/molecules31203641", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13707829/?tool=EBI", "id": "0h68c7xy5zd67", "issns": [ "1420-3049" ], "landing_url": "https://hal.science/hal-05804817v1", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "hal", "0.chim" ], [ "openalex", "2707|Natural Compounds in Disease Treatment" ] ], "openalex": "W7221503334", "pdf_url": "https://hal.science/hal-05804817/document", "pmcid": "PMC13707829", "pmid": null, "published": "2026-10-01", "publisher": "MDPI", "ris": "https://research.draconitic.com/paper/0h68c7xy5zd67.ris", "sources": [ { "first_seen": "2026-10-30T12:18:03Z", "native_id": "hal-05804817", "source": "hal", "url": "https://hal.science/hal-05804817v1" }, { "first_seen": "2026-10-30T12:18:42Z", "native_id": "10.3390/molecules31203641", "source": "crossref", "url": "https://www.mdpi.com/1420-3049/31/20/3641" }, { "first_seen": "2026-10-30T12:21:40Z", "native_id": "PMC:PMC13707829", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13707829" } ], "subjects": [ { "field": "chemistry", "origin": "hal:0.chim", "subfield": "general" } ], "title": "Celastrol and Its Derivatives in Breast, Ovarian, and Cervical Cancer: Molecular Targets, Signalling Networks, and Nanocarrier-Based Delivery", "title_text": "Celastrol and Its Derivatives in Breast, Ovarian, and Cervical Cancer: Molecular Targets, Signalling Networks, and Nanocarrier-Based Delivery", "type": "peer-reviewed", "updated_at": "2026-10-31T12:20:56Z", "url": "https://research.draconitic.com/paper/0h68c7xy5zd67", "venue": "Molecules", "versions": [] }