CDC7激酶抑制剂:近期专利文献综述(2017-2022)。

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Expert Opinion on Therapeutic Patents Pub Date : 2023-07-01 Epub Date: 2023-11-06 DOI:10.1080/13543776.2023.2262138
Takayuki Irie, Masaaki Sawa
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引用次数: 0

摘要

简介:CDC7是一种丝氨酸/苏氨酸激酶,在DNA复制中起重要作用。在癌症细胞中抑制CDC7会导致致命的S期或M期进展,而在正常细胞中抑制CD C7不会导致细胞死亡,只会导致DNA复制检查点的细胞周期停滞。因此,CDC7已被认为是癌症新的治疗干预措施的潜在靶点。所涵盖的领域:2017年至2022年披露的声称具有抑制CDC7的新型小分子化合物的专利文献。专家意见:尽管CDC7作为药物靶点具有无可争议的积极影响,但据报道,只有少数化学支架作为CDC7抑制剂。几种CDC7抑制剂已进入癌症治疗的临床试验,但在这些试验中没有产生令人满意的疗效。失败的一个可能原因可能是剂量限制毒性,一些观察到的毒性被认为与CDC7抑制无关,这表明识别新的化学支架以消除不必要的毒性应该很重要。另一个重要因素是患者分层,这将使反应更大,而这种预测性生物标志物的识别应该是CDC7抑制剂开发成功的关键。
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CDC7 kinase inhibitors: a survey of recent patent literature (2017-2022).

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.

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来源期刊
CiteScore
12.10
自引率
1.50%
发文量
50
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Therapeutic Patents (ISSN 1354-3776 [print], 1744-7674 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on recent pharmaceutical patent claims, providing expert opinion the scope for future development, in the context of the scientific literature. The Editors welcome: Reviews covering recent patent claims on compounds or applications with therapeutic potential, including biotherapeutics and small-molecule agents with specific molecular targets; and patenting trends in a particular therapeutic area Patent Evaluations examining the aims and chemical and biological claims of individual patents Perspectives on issues relating to intellectual property The audience consists of scientists, managers and decision-makers in the pharmaceutical industry and others closely involved in R&D Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days.
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