• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

CDK7 激酶抑制剂:对近年专利文献(2017-2022 年)的调查。

CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022).

机构信息

Drug Discovery and Development, Carna Biosciences, Inc, Kobe, Japan.

出版信息

Expert Opin Ther Pat. 2023 Jul-Dec;33(7-8):493-501. doi: 10.1080/13543776.2023.2262138. Epub 2023 Nov 6.

DOI:10.1080/13543776.2023.2262138
PMID:37735909
Abstract

INTRODUCTION

CDC7 is a serine/threonine kinase which plays an important role in DNA replication. Inhibition of CDC7 in cancer cells causes lethal S phase or M phase progression, whereas inhibition of CDC7 in normal cells does not cause cell death and only leads to cell cycle arrest at the DNA replication checkpoint. Therefore, CDC7 has been recognized as a potential target for novel therapeutic interventions in cancers.

AREAS COVERED

Patent literature claiming novel small molecule compounds inhibiting CDC7 disclosed from 2017 to 2022.

EXPERT OPINION

Despite the indisputable positive impact of CDC7 as a drug target, there have been reported only a handful of chemical scaffolds as CDC7 inhibitors. Several CDC7 inhibitors have been progressed into clinical trials for cancer treatments, but they did not result in satisfactory efficacies in those trials. One possible reason for the failure might be due to the dose-limiting toxicities, and some of the observed toxicities were thought to be not related to CDC7 inhibition, suggesting it should be important to identify novel chemical scaffolds to eliminate unwanted toxicities. Another important factor is the patient stratification that would enable greater response, and the identification of such predictive biomarkers should be the key to success for the development of CDC7 inhibitors.

摘要

简介

CDC7 是一种丝氨酸/苏氨酸激酶,在 DNA 复制中发挥重要作用。在癌细胞中抑制 CDC7 会导致致命的 S 期或 M 期进展,而在正常细胞中抑制 CDC7 不会导致细胞死亡,只会导致细胞周期在 DNA 复制检查点停滞。因此,CDC7 已被认为是癌症新型治疗干预的潜在靶点。

涵盖领域

2017 年至 2022 年期间,申报了新型小分子化合物抑制 CDC7 的专利文献。

专家意见

尽管 CDC7 作为药物靶点具有不可否认的积极影响,但作为 CDC7 抑制剂的化学结构骨架却寥寥无几。一些 CDC7 抑制剂已进入癌症治疗的临床试验,但在这些试验中并未取得令人满意的疗效。失败的一个可能原因可能是由于剂量限制毒性,并且一些观察到的毒性被认为与 CDC7 抑制无关,这表明消除不必要毒性的重要性在于确定新型化学结构骨架。另一个重要因素是患者分层,这将使更大的反应成为可能,而此类预测性生物标志物的鉴定应是开发 CDC7 抑制剂成功的关键。

相似文献

1
CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022).CDK7 激酶抑制剂:对近年专利文献(2017-2022 年)的调查。
Expert Opin Ther Pat. 2023 Jul-Dec;33(7-8):493-501. doi: 10.1080/13543776.2023.2262138. Epub 2023 Nov 6.
2
Identification of Novel Cdc7 Kinase Inhibitors as Anti-Cancer Agents that Target the Interaction with Dbf4 by the Fragment Complementation and Drug Repositioning Approach.通过片段互补和药物重定位方法鉴定新型 Cdc7 激酶抑制剂作为以 Dbf4 相互作用为靶点的抗癌剂。
EBioMedicine. 2018 Oct;36:241-251. doi: 10.1016/j.ebiom.2018.09.030. Epub 2018 Oct 5.
3
Targeting DNA replication before it starts: Cdc7 as a therapeutic target in p53-mutant breast cancers.在 DNA 复制开始之前靶向它:Cdc7 作为 p53 突变型乳腺癌的治疗靶点。
Am J Pathol. 2010 Oct;177(4):2034-45. doi: 10.2353/ajpath.2010.100421. Epub 2010 Aug 19.
4
Inhibition of checkpoint kinase 1 following gemcitabine-mediated S phase arrest results in CDC7- and CDK2-dependent replication catastrophe.吉西他滨介导的 S 期阻滞后抑制检查点激酶 1 导致 CDC7 和 CDK2 依赖性复制灾难。
J Biol Chem. 2019 Feb 8;294(6):1763-1778. doi: 10.1074/jbc.RA118.005231. Epub 2018 Dec 20.
5
Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.由于DNA起始激活检查点的废除,Cdc7是胰腺癌中一个有效的抗癌靶点。
Oncotarget. 2016 Apr 5;7(14):18495-507. doi: 10.18632/oncotarget.7611.
6
CDC7 as a novel biomarker and druggable target in cancer.CDC7 作为癌症的新型生物标志物和可用药靶。
Clin Transl Oncol. 2022 Oct;24(10):1856-1864. doi: 10.1007/s12094-022-02853-4. Epub 2022 Jun 3.
7
Cdc7-dependent and -independent phosphorylation of Claspin in the induction of the DNA replication checkpoint.Cdc7 依赖性和非依赖性的 Claspin 磷酸化在诱导 DNA 复制检查点中的作用。
Cell Cycle. 2013 May 15;12(10):1560-8. doi: 10.4161/cc.24675. Epub 2013 Apr 17.
8
High levels of Cdc7 and Dbf4 proteins can arrest cell-cycle progression.高水平的Cdc7和Dbf4蛋白可阻止细胞周期进程。
Eur J Cell Biol. 2005 Dec;84(12):927-38. doi: 10.1016/j.ejcb.2005.09.016. Epub 2005 Oct 26.
9
Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development.哺乳动物Cdc7激酶在DNA复制起始/监测及发育中的功能。
Mutat Res. 2003 Nov 27;532(1-2):29-40. doi: 10.1016/j.mrfmmm.2003.08.008.
10
Cdc7 kinase - a new target for drug development.Cdc7 激酶——药物研发的新靶点。
Eur J Cancer. 2010 Jan;46(1):33-40. doi: 10.1016/j.ejca.2009.09.020.

引用本文的文献

1
GmCDC7 is involved in coordinating seed size and quality in soybean.GmCDC7参与调控大豆种子的大小和质量。
Theor Appl Genet. 2025 Sep 19;138(10):253. doi: 10.1007/s00122-025-05039-y.
2
miRTARGET: An integrated web tool for the identification of microRNA targets with potential therapeutic or prognostic value in cancer.miRTARGET:一种用于识别在癌症中具有潜在治疗或预后价值的微小RNA靶点的综合网络工具。
Neoplasia. 2025 Jun 24;67:101202. doi: 10.1016/j.neo.2025.101202.
3
Experimental, Theoretical, and Studies of Potential CDC7 Kinase Inhibitors.
CDC7激酶潜在抑制剂的实验、理论及相关研究
ACS Omega. 2024 Dec 31;10(1):609-618. doi: 10.1021/acsomega.4c07221. eCollection 2025 Jan 14.
4
CDC7 Inhibition Potentiates Antitumor Efficacy of PARP Inhibitor in Advanced Ovarian Cancer.CDC7抑制增强PARP抑制剂在晚期卵巢癌中的抗肿瘤疗效。
Adv Sci (Weinh). 2024 Dec;11(45):e2403782. doi: 10.1002/advs.202403782. Epub 2024 Oct 16.