PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.

IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL
Dipanjan Karati, Ankur Saha, Souvik Roy, Swarupananda Mukherjee
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引用次数: 0

Abstract

Cancer involves the uncontrolled, abnormal growth of cells and affects other tissues. Kinase has an impact on proliferating the cells and causing cancer. For the purpose of treating cancer, PIM kinase is a potential target. The pro-viral Integration site for moloney murine leukaemia virus (PIM) kinases is responsible for the tumorigenesis, by phosphorylating the proteins that control the cell cycle and cell proliferation. PIM-1, PIM-2, and PIM-3 are the three distinct isoforms of PIM kinases. The JAK/STAT pathway is essential for controlling how PIM genes are expressed. PIM kinase is also linked withPI3K/AKT/mTOR pathway in various types of cancers. The overexpression of PIM kinase will cause cancer. Currently, there are significant efforts being made in medication design and development to target its inhibition. A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. PIM kinase antagonists have a remarkable effect on different types of cancer. Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence. On the other hand, in recent years, it has aided in hastening the identification of multiple new PIM inhibitors. Cyanopyridines and Pyrazolo[1,5-a]pyrimidinecan act as potent PIM kinase inhibitors for cancer therapy. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer.

将 PIM 激酶抑制剂作为癌症治疗的新型治疗支架。
癌症涉及细胞不受控制的异常生长,并影响其他组织。激酶对细胞增殖和致癌有影响。为了治疗癌症,PIM 激酶是一个潜在的靶点。小鼠白血病病毒(PIM)激酶的亲病毒整合位点通过使控制细胞周期和细胞增殖的蛋白质磷酸化而导致肿瘤发生。PIM-1、PIM-2 和 PIM-3 是 PIM 激酶的三种不同异构体。JAK/STAT 通路对控制 PIM 基因的表达方式至关重要。在各种癌症中,PIM 激酶还与PI3K/AKT/mTOR 通路有关。PIM 激酶的过度表达会导致癌症。目前,针对抑制 PIM 激酶的药物设计和开发正在进行大量工作。目前已发现一些专门针对 PIM 蛋白的三磷酸腺苷(ATP)结合域的小型化学抑制剂(如 SGI-1776、AZD1208 和 LGH447)。PIM 激酶拮抗剂对不同类型的癌症有显著疗效。尽管第一种 PIM 抑制剂 SGI-1776 已进行了临床试验,但由于过早撤回,因此无法产生概念证据。另一方面,近年来,它又加速了多种新的 PIM 抑制剂的发现。氰基吡啶和吡唑并[1,5-a]嘧啶可作为有效的 PIM 激酶抑制剂用于癌症治疗。我们探讨了致癌转录因子 c-Mycandmi-RNA 与 PIM 激酶的关系。在本文中,我们重点介绍了 PIM 激酶的致癌作用,以及治疗癌症的 PIM 激酶抑制剂的结构见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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