通过过度表达Pim-1调节衰老、细胞周期、细胞凋亡和转移侵袭的异常信号转导:来自海洋的新抗癌靶点及其强效抑制剂

Ankita Sharma, S. Nandi
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引用次数: 2

摘要

现有的癌症化疗药物既能杀死正常细胞,也能杀死恶性细胞。为了解决这些问题,科学家们现在更关注的是设计和发现潜在的抗癌、毒性最小的铅,这些铅可以通过与衰老、细胞周期、细胞凋亡和转移性侵袭相关的原癌基因和肿瘤抑制基因的过度表达或突变而导致pm -1等蛋白激酶的超激活,从而促进细胞凋亡过程和抑制异常信号转导,从而产生抗癌活性。天然支架在这方面发挥了很大的作用。海洋充满了生物多样性的天然资源,药用化合物来源于海洋植物、海绵、放线菌、藻杆菌、真菌、珊瑚和动物。许多抗癌化合物被成功地发现。但针对异常信号转导机制的有效化合物很少。因此,本文将重点探讨pm -1过表达介导衰老、细胞周期、细胞凋亡和转移性侵袭的各种靶点及其有效抑制剂的分子机制。本文讨论了有效的海洋源抑制剂对异常信号转导保持活性的生化机制。它非常重视在这些即将到来的领域扩大能力,以保持全球相关性。本研究列出的现有海洋抗癌化合物可以作为模板,通过药物重定位的高通量筛选,进一步设计和合成有前途的抗其他疾病的同类合成化合物。
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Abnormal Signal Transduction via Over-expression of Pim-1 Regulated Senescence, Cell Cycle, Apoptosis and Metastatic Invasion: Novel Anticancer Targets and Their Potent Inhibitors from Marine Sources
Existing cancer chemotherapeutics can kill normal as well as malignant cells. To solve these issues, scientists are now more concerned about the design and discovery of potential anticancer, least toxic leads, which can promote apoptosis process and inhibition of abnormal signal transduction via hyperactivation of protein kinases such as Pim-1 due to overexpression or mutation of proto-oncogenes and tumor suppressor genes related to molecular mechanisms of senescence, cell cycle, apoptosis and metastatic invasion, thus leading to anticancer activities. Natural scaffolds play a great role in this aspect. Sea is full of biodiverse natural resources of medicinal compounds derived from marine plants, sponges, actinomycetes, cynobacteria, fungi, corals and animals. Many anticancer compounds were successfully discovered. But there are few potent compounds developed against abnormal signal transduction mechanism. Therefore, an attempt has been made in the present review to focus on molecular mechanisms of various targets in connection with the over-expression of Pim-1 mediated senescence, cell cycle, apoptosis and metastatic invasion and their potent inhibitors. Biochemical mechanisms of the potent marine sourced inhibitors keeping activities against abnormal signal transduction were discussed in this study. It gives great attention to expand the capabilities in these upcoming areas to remain globally relevant. Existed marine sourced anticancer compounds tabulated in this study could be used as a template for further design and synthesis of promising congeneric synthetic compounds against another disease by the application of in silico high throughput screening through drug repositioning.
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来源期刊
CiteScore
1.70
自引率
0.00%
发文量
18
审稿时长
>12 weeks
期刊介绍: In recent years a breakthrough has occurred in our understanding of the molecular pathomechanisms of human diseases whereby most of our diseases are related to intra and intercellular communication disorders. The concept of signal transduction therapy has got into the front line of modern drug research, and a multidisciplinary approach is being used to identify and treat signaling disorders. The journal publishes timely in-depth reviews, research article and drug clinical trial studies in the field of signal transduction therapy. Thematic issues are also published to cover selected areas of signal transduction therapy. Coverage of the field includes genomics, proteomics, medicinal chemistry and the relevant diseases involved in signaling e.g. cancer, neurodegenerative and inflammatory diseases. Current Signal Transduction Therapy is an essential journal for all involved in drug design and discovery.
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