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抗精神病药物五氟利多对致癌通道Kv10.1的抑制作用。

Inhibition of the oncogenic channel Kv10.1 by the antipsychotic drug penfluridol.

作者信息

León-Sánchez Paulina, Cedillo-Hernández Andrea Lizeth, Durán-Pastén María Luisa, Lara-Figueroa Cesar Oliver, Hernández-Cruz Arturo, Luis Enoch

机构信息

Laboratorio Nacional de Canalopatías, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.

Departamento de Neuropatología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.

出版信息

Front Pharmacol. 2025 Sep 3;16:1655406. doi: 10.3389/fphar.2025.1655406. eCollection 2025.

Abstract

Drug repurposing is an increasingly recognized strategy in pharmaceutical development that focuses on identifying new therapeutic uses for already approved drugs, as an alternative to the time-consuming and costly process of developing new molecular entities. This approach has gained traction in oncology, especially in exploring the anticancer potential of non-oncologic agents. In recent years, the antipsychotic drug penfluridol (PNFL) has been identified as having antitumoral properties; however, the underlying mechanisms remain poorly understood. We hypothesized that PNFL may exert its effects by inhibiting the oncogenic potassium channel Kv10.1. Our results demonstrate that PNFL inhibits Kv10.1 activity and reduces cell migration in HEK-Kv10.1 cells. These findings suggest a novel mechanism that may contribute to the drug's antitumoral effects.

摘要

药物重新利用是药物研发中一种日益受到认可的策略,该策略专注于为已获批药物确定新的治疗用途,以此替代开发新分子实体耗时且成本高昂的过程。这种方法在肿瘤学领域已获得关注,尤其是在探索非肿瘤药物的抗癌潜力方面。近年来,抗精神病药物五氟利多(PNFL)已被确定具有抗肿瘤特性;然而,其潜在机制仍知之甚少。我们推测PNFL可能通过抑制致癌钾通道Kv10.1发挥作用。我们的结果表明,PNFL抑制Kv10.1活性并减少HEK-Kv10.1细胞的迁移。这些发现提示了一种可能有助于该药物抗肿瘤作用的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad7/12440886/e3f56df88a3e/fphar-16-1655406-g001.jpg

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