Tranoy-Opalinski Isabelle, Legigan Thibaut, Barat Romain, Clarhaut Jonathan, Thomas Mikaël, Renoux Brigitte, Papot Sébastien
Université de Poitiers, UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers (IC2MP), Groupe "Systèmes Moléculaires Programmés", 4 rue Michel Brunet, 86022 Poitiers, France.
Université de Poitiers, UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers (IC2MP), Groupe "Systèmes Moléculaires Programmés", 4 rue Michel Brunet, 86022 Poitiers, France; INSERM CIC 0802, CHU de Poitiers, 2 rue de la Milétrie, 86021 Poitiers, France.
Eur J Med Chem. 2014 Mar 3;74:302-13. doi: 10.1016/j.ejmech.2013.12.045. Epub 2014 Jan 11.
The design of novel antitumor agents allowing the destruction of malignant cells while sparing healthy tissues is one of the major challenges in medicinal chemistry. In this context, the use of non-toxic prodrugs programmed to be selectively activated by beta-glucuronidase present at high concentration in the microenvironment of most solid tumors has attracted considerable attention. This review summarizes the major progresses that have been realized in this field over the past ten years. This includes the new prodrugs that have been designed to target a wide variety of anticancer drugs, the prodrugs employed in the course of a combined therapy, the dendritic glucuronide prodrugs and the concept of β-glucuronidase-responsive albumin binding prodrugs.
设计新型抗肿瘤药物，使其能够在不损伤健康组织的前提下破坏恶性细胞，是药物化学领域的主要挑战之一。在此背景下，利用无毒前药，使其在大多数实体瘤微环境中高浓度存在的β-葡萄糖醛酸酶作用下被选择性激活，已引起了广泛关注。本综述总结了过去十年该领域取得的主要进展。这包括设计用于多种抗癌药物的新型前药、联合治疗过程中使用的前药、树枝状葡萄糖醛酸前药以及β-葡萄糖醛酸酶响应性白蛋白结合前药的概念。
