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抗逆转录病毒药物利匹韦林的演变和肿瘤学方法。

Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.

机构信息

OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), 4200-450 Porto, Portugal.

CINTESIS@RISE, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.

出版信息

Int J Mol Sci. 2023 Feb 2;24(3):2890. doi: 10.3390/ijms24032890.

Abstract

Rilpivirine is an antiretroviral drug used to treat AIDS worldwide. The drug is a non-nucleoside reverse transcriptase inhibitor that halts the cDNA elongation process and, thus, the capacity of the HIV-1 virus to replicate. With the new wave of drug repurposing in recent years, rilpivirine has been studied in this regard. This drug is useful in Zika virus treatment, with in vivo results indicating regression in neuronal effects often associated with this infection. Several cancer types have also been researched, from breast to leukemia and pancreatic cancer, and rilpivirine has proved to have inhibitory effects in various cell lines with low concentrations, causing cellular death, apoptosis, and cell cycle arrest. The pathways are not yet established, but some works have hypothesized and demonstrated that rilpivirine causes inhibition of Aurora A kinase and has effects on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and the vascular endothelial growth factors-receptors (VEGFs-VEGFRs) pathway, which are known to be altered in cancer and tumors and can be targeted for cancer treatment. Further testing and clinical trials are needed, but this review demonstrates the potential of rilpivirine's repurposing for cancer treatment.

摘要

利匹韦林是一种用于治疗艾滋病的抗逆转录病毒药物,在全球范围内使用。该药物是一种非核苷类逆转录酶抑制剂,可阻止 cDNA 延伸过程,从而阻止 HIV-1 病毒的复制。近年来,随着药物再利用的新浪潮,利匹韦林在这方面得到了研究。该药物在寨卡病毒治疗中有用,体内结果表明,神经元效应常与这种感染相关的逆转。还研究了几种癌症类型,从乳腺癌到白血病和胰腺癌,利匹韦林已被证明在低浓度下对各种细胞系具有抑制作用,导致细胞死亡、细胞凋亡和细胞周期停滞。其途径尚未确定,但一些研究工作假设并证明,利匹韦林抑制 Aurora A 激酶,并对 Janus 激酶信号转导和转录激活因子(JAK-STAT)信号通路和血管内皮生长因子受体(VEGFs-VEGFRs)通路产生影响,这些通路在癌症和肿瘤中发生改变,可以作为癌症治疗的靶点。还需要进一步的测试和临床试验,但本综述证明了利匹韦林在癌症治疗中的再利用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e05/9917964/3d4acec6f01d/ijms-24-02890-g001.jpg

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