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系统综述:理解天然 CDK 抑制剂在癌症进展中的作用机制途径和临床方面:揭示细胞和生化机制。

A systematic review on understanding the mechanistic pathways and clinical aspects of natural CDK inhibitors on cancer progression.: Unlocking cellular and biochemical mechanisms.

机构信息

Institute of Pharmaceutical Sciences (IPS), University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan.

Institute of Pharmaceutical Sciences (IPS), University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan.

出版信息

Chem Biol Interact. 2024 Apr 25;393:110940. doi: 10.1016/j.cbi.2024.110940. Epub 2024 Mar 11.

Abstract

Cell division, differentiation, and controlled cell death are all regulated by phosphorylation, a key biological function. This mechanism is controlled by a variety of enzymes, with cyclin-dependent kinases (CDKs) being particularly important in phosphorylating proteins at serine and threonine sites. CDKs, which contain 20 unique components, serve an important role in regulating vital physiological functions such as cell cycle progression and gene transcription. Methodologically, an extensive literature search was performed using reputable databases such as PubMed, Google Scholar, Scopus, and Web of Science. Keywords encompassed "cyclin kinase," "cyclin dependent kinase inhibitors," "CDK inhibitors," "natural products," and "cancer therapy." The inclusion criteria, focused on relevance, publication date, and language, ensured a thorough representation of the most recent research in the field, encompassing articles published from January 2015 to September 2023. Categorization of CDKs into those regulating transcription and those orchestrating cell cycle phases provides a comprehensive understanding of their diverse functions. Ongoing clinical trials featuring CDK inhibitors, notably CDK7 and CDK4/6 inhibitors, illuminate their promising potential in various cancer treatments. This review undertakes a thorough investigation of CDK inhibitors derived from natural (marine, terrestrial, and peptide) sources. The aim of this study is to provide a comprehensive comprehension of the chemical classifications, origins, target CDKs, associated cancer types, and therapeutic applications.

摘要

细胞分裂、分化和受控细胞死亡均受磷酸化调控,这是一种关键的生物学功能。该机制由多种酶控制,其中细胞周期蛋白依赖性激酶(CDKs)在丝氨酸和苏氨酸位点磷酸化蛋白质方面尤为重要。CDKs 包含 20 种独特成分,在调节细胞周期进程和基因转录等重要生理功能方面发挥着重要作用。在方法学上,使用 PubMed、Google Scholar、Scopus 和 Web of Science 等知名数据库进行了广泛的文献检索。关键词包括“细胞周期蛋白激酶”、“细胞周期蛋白依赖性激酶抑制剂”、“CDK 抑制剂”、“天然产物”和“癌症治疗”。纳入标准侧重于相关性、出版日期和语言,以确保对该领域最新研究的全面代表,涵盖了 2015 年 1 月至 2023 年 9 月发表的文章。将 CDKs 分为调节转录的 CDK 和协调细胞周期阶段的 CDK,可全面了解它们的多种功能。目前正在进行的以 CDK 抑制剂(尤其是 CDK7 和 CDK4/6 抑制剂)为特色的临床试验表明了它们在各种癌症治疗中的应用前景。本综述对天然(海洋、陆地和肽)来源的 CDK 抑制剂进行了全面调查。本研究的目的是全面了解化学分类、来源、靶标 CDK、相关癌症类型和治疗应用。

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