Department of Pharmaceutical Technology, School of Pharmacy, Techno India University, Kolkata 700091, West Bengal, India.
Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata - Group of Institutions, 124, B.L Saha Road, Kolkata 700053, West Bengal, India.
Curr Top Med Chem. 2024;24(28):2489-2508. doi: 10.2174/0115680266321659240906114742.
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 Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence.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.
癌症涉及细胞的不受控制的异常生长,并影响其他组织。激酶对细胞的增殖和致癌有影响。为了治疗癌症,PIM 激酶是一个潜在的靶点。莫洛尼鼠白血病病毒(MoMLV)前病毒整合位点(PIM)激酶通过磷酸化控制细胞周期和细胞增殖的蛋白质,导致肿瘤发生。PIM-1、PIM-2 和 PIM-3 是 PIM 激酶的三种不同同工型。JAK/STAT 途径对于控制 PIM 基因的表达至关重要。PIM 激酶还与多种类型的癌症中的 PI3K/AKT/mTOR 途径有关。PIM 激酶的过表达会导致癌症。目前,正在进行药物设计和开发方面的大量努力,以靶向其抑制。已经鉴定出几种专门针对 PIM 蛋白三磷酸腺苷(ATP)结合域的小分子化学抑制剂(例如 SGI-1776、AZD1208、LGH447)。PIM 激酶拮抗剂对不同类型的癌症有显著的效果。尽管对第一个 PIM 抑制剂 SGI-1776 进行了临床试验,但该药被过早撤回,因此无法产生概念证据。另一方面,近年来,它有助于加速鉴定多种新的 PIM 抑制剂。氰基吡啶和吡唑并[1,5-a]嘧啶可作为癌症治疗的有效 PIM 激酶抑制剂。我们探讨了致癌转录因子 c-Myc 和 miRNA 与 PIM 激酶的关系。在本文中,我们强调了 PIM 激酶抑制剂的致癌作用和结构见解,以治疗癌症。