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用于肿瘤治疗的双PI3K/mTOR抑制剂的最新进展

Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.

作者信息

Wu Xianbo, Xu Yihua, Liang Qi, Yang Xinwei, Huang Jianli, Wang Jie, Zhang Hong, Shi Jianyou

机构信息

School of Sports Medicine and Health, Chengdu Sport University, Chengdu, China.

School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Front Pharmacol. 2022 May 9;13:875372. doi: 10.3389/fphar.2022.875372. eCollection 2022.

Abstract

The PI3K-Akt-mTOR pathway is a viable target for cancer treatment and can be used to treat various malignant tumours, including follicular lymphoma and breast cancer. Both enzymes, PI3K and mTOR, are critical in this pathway. Hence, in recent years, an array of inhibitors targeting these two targets have been studied, showing dual PI3K/mTOR inhibition compared with single targeting small molecule inhibitors. Inhibitors not only inhibit cell proliferation but also promote cell apoptosis. These inhibitors show high potency and little drug resistance even at low doses, suggesting that PI3K/mTOR inhibitors are promising cancer drugs. Herein, we summarised the recent research of PI3K/mTOR dual inhibitors-for example, structure-activity relationship, pharmacokinetics, and clinical practice, and briefly commented on them. https://clinicaltrials.gov.

摘要

PI3K-Akt-mTOR信号通路是癌症治疗的一个可行靶点,可用于治疗各种恶性肿瘤,包括滤泡性淋巴瘤和乳腺癌。PI3K和mTOR这两种酶在该信号通路中都至关重要。因此,近年来,一系列针对这两个靶点的抑制剂已被研究,与单靶点小分子抑制剂相比,显示出双重PI3K/mTOR抑制作用。这些抑制剂不仅抑制细胞增殖,还促进细胞凋亡。即使在低剂量下,这些抑制剂也显示出高效力和低耐药性,这表明PI3K/mTOR抑制剂是很有前景的抗癌药物。在此,我们总结了PI3K/mTOR双重抑制剂的最新研究——例如,构效关系、药代动力学和临床应用,并对其进行了简要评论。https://clinicaltrials.gov

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5f9/9124774/d4e5cfa7ff08/fphar-13-875372-g001.jpg

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