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聚焦AKT:当前的治疗挑战。

Spotlight on AKT: Current Therapeutic Challenges.

作者信息

Landel Ina, Quambusch Lena, Depta Laura, Rauh Daniel

机构信息

Faculty of Chemistry and Chemical Biology, TU Dortmund University and Drug Discovery Hub Dortmund (DDHD), Zentrum für Wirkstoffforschung (ZIW), Otto-Hahn-Strasse 4a, 44227 Dortmund, Germany.

出版信息

ACS Med Chem Lett. 2020 Mar 12;11(3):225-227. doi: 10.1021/acsmedchemlett.9b00548.

DOI:10.1021/acsmedchemlett.9b00548
PMID:32184947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7073864/
Abstract

The protein kinase B (Akt) exemplifies an important switch of cell death and survival within the PI3K/Akt signaling pathway, which renders Akt a valuable target in diseases such as cancer. Herein, we give a short overview of clinical applications involving Akt, outline promising and innovative approaches to investigate the role of this kinase in diseases, and highlight the current challenges that require thorough investigation to set the groundwork for successful therapeutic strategies.

摘要

蛋白激酶B(Akt)是PI3K/Akt信号通路中细胞死亡和存活的重要开关,这使得Akt成为癌症等疾病中有价值的靶点。在此,我们简要概述涉及Akt的临床应用,概述研究该激酶在疾病中作用的有前景和创新性方法,并强调当前需要深入研究以奠定成功治疗策略基础的挑战。

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本文引用的文献

1
Covalent-Allosteric Inhibitors to Achieve Akt Isoform-Selectivity.实现 Akt 同工型选择性的共价变构抑制剂。
Angew Chem Int Ed Engl. 2019 Dec 19;58(52):18823-18829. doi: 10.1002/anie.201909857. Epub 2019 Nov 8.
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Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation.PIK3CA 或 AKT 突变和/或 PTEN 缺失/PTEN 突变的晚期乳腺癌患者中 AKT 抑制剂 MK-2206 的 II 期临床试验。
Breast Cancer Res. 2019 Jul 5;21(1):78. doi: 10.1186/s13058-019-1154-8.
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First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma.首例米哚妥林治疗青少年 Proteus 综合征合并卵巢癌的疗效证据。
Am J Med Genet A. 2019 Jul;179(7):1319-1324. doi: 10.1002/ajmg.a.61160. Epub 2019 May 6.
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Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt.对蛋白激酶Akt共价变构抑制的结构与化学见解。
Chem Sci. 2019 Feb 13;10(12):3573-3585. doi: 10.1039/c8sc05212c. eCollection 2019 Mar 28.
5
Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in -Mutant Pancreatic and Colorectal Cancer.在 - 突变型胰腺和结直肠癌中,共价变构 AKT 抑制剂 Borussertib 与 Trametinib 联合的临床前疗效。
Cancer Res. 2019 May 1;79(9):2367-2378. doi: 10.1158/0008-5472.CAN-18-2861. Epub 2019 Mar 11.
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The Akt pathway in oncology therapy and beyond (Review).肿瘤治疗领域中 Akt 通路的研究进展及其相关应用(综述)。
Int J Oncol. 2018 Dec;53(6):2319-2331. doi: 10.3892/ijo.2018.4597. Epub 2018 Oct 16.
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AKT Inhibition in Solid Tumors With AKT1 Mutations.对携带AKT1突变的实体瘤进行AKT抑制
J Clin Oncol. 2017 Jul 10;35(20):2251-2259. doi: 10.1200/JCO.2017.73.0143. Epub 2017 May 10.
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A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors.ATP竞争性AKT抑制剂ipatasertib的首次人体I期研究表明,在实体瘤患者中对AKT进行了有效且安全的靶向治疗。
Cancer Discov. 2017 Jan;7(1):102-113. doi: 10.1158/2159-8290.CD-16-0512. Epub 2016 Nov 21.
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AKT in cancer: new molecular insights and advances in drug development.AKT与癌症:药物研发中的新分子见解与进展
Br J Clin Pharmacol. 2016 Oct;82(4):943-56. doi: 10.1111/bcp.13021. Epub 2016 Jun 27.
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Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review).Akt抑制剂在癌症治疗中的应用:从药物发现到临床应用的漫长历程(综述)
Int J Oncol. 2016 Mar;48(3):869-85. doi: 10.3892/ijo.2015.3306. Epub 2015 Dec 24.