title: Synthesis and antitumor efficacy of a β-glucuronidase-responsive albumin-binding prodrug of doxorubicin.
abstract: In this paper we describe the synthesis and biological evaluation of the first β-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug.
authors.affiliation: Institut de Chimie des Milieux et des Matériaux de Poitiers, IC2MP, Université de Poitiers, UMR-CNRS 7285, 4 Rue Michel Brunet, 86022 Poitiers, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Legigan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clarhaut
authors.forename: Brigitte
authors.initials: B
authors.lastname: Renoux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tranoy-Opalinski
authors.forename: Arnaud
authors.initials: A
authors.lastname: Monvoisin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Berjeaud
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
authors.forename: Sébastien
authors.initials: S
authors.lastname: Papot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006027:Glycosides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008301:Maleimides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D021241:Spectrometry, Mass, Electrospray Ionization; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D008301:Maleimides; D011355:Prodrugs; D011092:Polyethylene Glycols; D004317:Doxorubicin