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直接 KRAS G12C 突变抑制剂的研究进展。

The Research Progress of Direct KRAS G12C Mutation Inhibitors.

机构信息

Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Pathol Oncol Res. 2021 Apr 23;27:631095. doi: 10.3389/pore.2021.631095. eCollection 2021.

DOI:10.3389/pore.2021.631095
PMID:34257597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8262225/
Abstract

KRAS mutations have long been considered undruggable. However, a series of direct KRAS mutation inhibitors have been developed since the switch II pocket was discovered recently. This review will summarize progress in the development of direct KRAS G12C mutation inhibitors, current relevant drugs under study and challenges that need to be considered in future research.

摘要

KRAS 突变长期以来被认为是不可成药的。然而,自从最近发现开关 II 口袋以来,已经开发出了一系列直接的 KRAS 突变抑制剂。这篇综述将总结直接 KRAS G12C 突变抑制剂的开发进展,目前正在研究的相关药物以及未来研究中需要考虑的挑战。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/d85af01d56f2/pore-27-631095-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/db0f7d6f5818/pore-27-631095-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/1a424f6485e8/pore-27-631095-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/321afff7b855/pore-27-631095-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/d85af01d56f2/pore-27-631095-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/db0f7d6f5818/pore-27-631095-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/58667398a77a/pore-27-631095-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/27f18ba7f6e6/pore-27-631095-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/1a424f6485e8/pore-27-631095-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/321afff7b855/pore-27-631095-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53fa/8262225/d85af01d56f2/pore-27-631095-g008.jpg

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本文引用的文献

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A bright future for KRAS inhibitors.KRAS抑制剂的光明未来。
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Cancer Treat Rev. 2020 Mar;84:101974. doi: 10.1016/j.ctrv.2020.101974. Epub 2020 Jan 23.
3
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition.快速非均匀适应构象特异性 KRAS(G12C)抑制。
靶向“不可成药”蛋白的最新进展:从药物发现到临床试验。
Signal Transduct Target Ther. 2023 Sep 6;8(1):335. doi: 10.1038/s41392-023-01589-z.
4
Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles.多种癌症逃避多种 MAPK 通路抑制剂,并利用 DNA 复制应激信号来耐受异常细胞周期。
Sci Signal. 2023 Aug;16(796):eade8744. doi: 10.1126/scisignal.ade8744. Epub 2023 Aug 1.
5
Potential biomarkers uncovered by bioinformatics analysis in sotorasib resistant-pancreatic ductal adenocarcinoma.通过生物信息学分析在索托拉西布耐药性胰腺导管腺癌中发现的潜在生物标志物。
Front Med (Lausanne). 2023 Jun 15;10:1107128. doi: 10.3389/fmed.2023.1107128. eCollection 2023.
6
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Oncotarget. 2023 Jul 1;14:672-687. doi: 10.18632/oncotarget.28469.
7
RAS degraders: The new frontier for RAS-driven cancers.RAS 降解剂:RAS 驱动型癌症的新前沿。
Mol Ther. 2023 Jul 5;31(7):1904-1919. doi: 10.1016/j.ymthe.2023.03.017. Epub 2023 Mar 21.
8
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Front Immunol. 2023 Feb 2;14:1063716. doi: 10.3389/fimmu.2023.1063716. eCollection 2023.
9
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Bioengineering (Basel). 2022 Dec 12;9(12):792. doi: 10.3390/bioengineering9120792.
10
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Nature. 2020 Jan;577(7790):421-425. doi: 10.1038/s41586-019-1884-x. Epub 2020 Jan 8.
4
Discovery of a Covalent Inhibitor of KRAS (AMG 510) for the Treatment of Solid Tumors.发现 KRAS(AMG 510)共价抑制剂用于治疗实体瘤。
J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.
5
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Eur J Med Chem. 2020 Jan 1;185:111844. doi: 10.1016/j.ejmech.2019.111844. Epub 2019 Nov 2.
6
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7
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