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将诱导细胞自噬的抗癌药物再用于驱虫治疗。

Repurposing methuosis-inducing anticancer drugs for anthelmintic therapy.

机构信息

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu, India.

Centre for Drug Discovery and Development (CD3), Amity Institute of Biotechnology, Amity University Maharashtra, Bhatan, Panvel, Mumbai, Maharashtra, India.

出版信息

PLoS Pathog. 2024 Sep 5;20(9):e1012475. doi: 10.1371/journal.ppat.1012475. eCollection 2024 Sep.

Abstract

Drug-resistant parasitic nematodes pose a grave threat to plants, animals, and humans. An innovative paradigm for treating parasitic nematodes is emphasized in this opinion. This approach relies on repurposing methuosis (a death characterized by accumulation of large vacuoles) inducing anticancer drugs as anthelmintics. We review drugs/chemicals that have shown to kill nematodes or cancerous cells by inducing multiple vacuoles that eventually coalesce and rupture. This perspective additionally offers a succinct summary on Structure-Activity Relationship (SAR) of methuosis-inducing small molecules. This strategy holds promise for the development of broad-spectrum anthelmintics, shedding light on shared molecular mechanisms between cancer and nematodes in response to these inducers, thereby potentially transforming both therapeutic domains.

摘要

耐药性寄生线虫对植物、动物和人类构成严重威胁。本观点强调了一种治疗寄生线虫的创新模式。该方法依赖于重新利用溶酶体(一种以大液泡积累为特征的死亡)诱导的抗癌药物作为驱虫药。我们回顾了一些已经证明可以通过诱导多个最终融合和破裂的液泡来杀死线虫或癌细胞的药物/化学物质。此外,本观点还简要总结了溶酶体诱导小分子的构效关系(SAR)。该策略有望开发广谱驱虫药,阐明线虫和癌症对这些诱导剂的反应之间的共同分子机制,从而有可能改变这两个治疗领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f269/11376546/221c87b818e1/ppat.1012475.g001.jpg

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