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近年来,针对神经胶质瘤的小分子药物研发取得了新进展。

Recent advances in the discovery of small molecules targeting glioblastoma.

机构信息

São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, 14800-903, Brazil; São Paulo State University (UNESP), Institute of Chemistry, Araraquara, 14800-060, Brazil.

São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, 14800-903, Brazil.

出版信息

Eur J Med Chem. 2019 Feb 15;164:8-26. doi: 10.1016/j.ejmech.2018.12.033. Epub 2018 Dec 16.

Abstract

Glioblastoma (GBM) is one of the most common central nervous system cancers. It is characterized as a fast-growing tumor that arises from multiple cell types with neural stem-cell-like properties. Additionally, GBM tumors are highly invasive, which is attributed to the presence of glioblastoma stem cells that makes surgery ineffective in most cases. Currently, temozolomide is the unique chemotherapy option approved by the U.S. Food and Drug Administration for GBM treatment. This review analyzes the emergence and development of new synthetic small molecules discovered as promising anti-glioblastoma agents. A number of compounds were described herein and grouped according to the main chemical class used in the drug discovery process. Importantly, we focused only on synthetic compounds published in the last 10 years, thus excluding natural products. Furthermore, we included in this review only those most biologically active compounds with proven in vitro and/or in vivo efficacy.

摘要

胶质母细胞瘤(GBM)是最常见的中枢神经系统癌症之一。它的特点是一种快速生长的肿瘤,来源于具有神经干细胞样特性的多种细胞类型。此外,GBM 肿瘤具有高度侵袭性,这归因于存在胶质母细胞瘤干细胞,这使得手术在大多数情况下无效。目前,替莫唑胺是美国食品和药物管理局唯一批准用于 GBM 治疗的化疗药物。本综述分析了作为有前途的抗胶质母细胞瘤药物而发现的新合成小分子的出现和发展。本文描述了许多化合物,并根据药物发现过程中使用的主要化学类别进行了分组。重要的是,我们只关注在过去 10 年中发表的合成化合物,因此排除了天然产物。此外,我们仅将那些具有已证明的体外和/或体内疗效的最具生物活性的化合物纳入本综述。

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