徐俊杰, 尤启冬, 郭小可. 靶向MYC小分子抑制剂的研究进展J. 药学学报, 2022,57(6): 1689-1701. doi: 10.16438/j.0513-4870.2021-1794
引用本文: 徐俊杰, 尤启冬, 郭小可. 靶向MYC小分子抑制剂的研究进展J. 药学学报, 2022,57(6): 1689-1701. doi: 10.16438/j.0513-4870.2021-1794
XU Jun-jie, YOU Qi-dong, GUO Xiao-ke. The development of small-molecule inhibitors targeting MYCJ. Acta Pharmaceutica Sinica, 2022,57(6): 1689-1701. doi: 10.16438/j.0513-4870.2021-1794
Citation: XU Jun-jie, YOU Qi-dong, GUO Xiao-ke. The development of small-molecule inhibitors targeting MYCJ. Acta Pharmaceutica Sinica, 2022,57(6): 1689-1701. doi: 10.16438/j.0513-4870.2021-1794

靶向MYC小分子抑制剂的研究进展

The development of small-molecule inhibitors targeting MYC

  • 摘要: MYC基因由3个旁系同源基因C-MYCN-MYCL-MYC组成,是人类癌症中最常见的失调驱动基因之一,在超过一半的癌症类型中被异常激活。由于MYC在癌症的形成、维持和发展中起着重要的作用,因此,靶向MYC蛋白是治疗癌症的一种有效的策略。但由于缺乏适合小分子配体进行结合的口袋,MYC蛋白被认为是“不可成药”的抗癌靶点。然而,近年来,相关蛋白质结构信息愈加丰富以及越来越多新型计算工具出现,衍生了许多间接靶向抑制MYC的策略,并在肿瘤模型中展现了不错的抗肿瘤效果。本文根据其作用机制,将目前的间接靶向MYC的小分子分为作用于MYC PPI (protein-protein interaction,蛋白-蛋白相互作用)的抑制剂和调控MYC作用的靶点抑制剂,并针对不同机制的化合物分别进行了介绍和评述,以期为MYC抑制剂的进一步研究提供参考。

     

    Abstract: The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.

     

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