SPPSPTM, SVKM's NMIMS, Mumbai, India.
Department of Medical Oncology, VU University Medical Centre, Amsterdam, The Netherlands.
Med Res Rev. 2020 Sep;40(5):1871-1919. doi: 10.1002/med.21674. Epub 2020 May 11.
Telomerase has emerged as an important primary target in anticancer therapy. It is a distinctive reverse transcriptase enzyme, which extends the length of telomere at the 3' chromosomal end, and uses telomerase reverse transcriptase (TERT) and telomerase RNA template-containing domains. Telomerase has a vital role and is a contributing factor in human health, mainly affecting cell aging and cell proliferation. Due to its unique feature, it ensures unrestricted cell proliferation in malignancy and plays a major role in cancer disease. The development of telomerase inhibitors with increased specificity and better pharmacokinetics is being considered to design and develop newer potent anticancer agents. Use of natural and synthetic compounds for the inhibition of telomerase activity can lead to an opening of new vistas in cancer treatment. This review details about the telomerase biochemistry, use of natural and synthetic compounds; vaccines and oncolytic virus in therapy that suppress the telomerase activity. We have discussed structure-activity relationships of various natural and synthetic telomerase inhibitors to help medicinal chemists and chemical biology researchers with a ready reference and updated status of their clinical trials. Suppression of human TERT (hTERT) activity through inhibition of hTERT promoter is an important approach for telomerase inhibition.
端粒酶已成为癌症治疗的一个重要的主要靶点。它是一种独特的逆转录酶,可在染色体 3'末端延长端粒的长度,并使用端粒酶逆转录酶(TERT)和含有端粒酶 RNA 模板的结构域。端粒酶在人类健康中起着至关重要的作用,主要影响细胞衰老和细胞增殖。由于其独特的特性,它确保了恶性肿瘤中不受限制的细胞增殖,并在癌症疾病中发挥着重要作用。正在考虑开发具有更高特异性和更好药代动力学的端粒酶抑制剂,以设计和开发新型有效的抗癌药物。使用天然和合成化合物抑制端粒酶活性可以为癌症治疗开辟新的前景。本综述详细介绍了端粒酶的生物化学、天然和合成化合物的应用、抑制端粒酶活性的疫苗和溶瘤病毒。我们讨论了各种天然和合成端粒酶抑制剂的构效关系,以帮助药物化学家和化学生物学研究人员作为参考,并及时了解它们的临床试验状况。通过抑制 hTERT 启动子抑制人端粒酶(hTERT)活性是抑制端粒酶的重要方法。