Advances in the research and application of neurokinin-1 receptor antagonists

Xiangyu HONG; Junjie MA; Shanshan ZHENG; Guangyu ZHAO; Caiyun FU

doi:10.1631/jzus.B2300455

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Review | Updated：2024-02-01

Advances in the research and application of neurokinin-1 receptor antagonists
Advances in the research and application of neurokinin-1 receptor antagonists
神经激肽1受体拮抗剂的研究与应用进展
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 2, Pages: 91-105(2024)
Affiliations：

College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
Funds：
DOI：10.1631/jzus.B2300455
CLC：
CSTR：

洪翔宇,马俊杰,郑珊珊等.神经激肽1受体拮抗剂的研究与应用进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(02):91-105.

Xiangyu HONG, Junjie MA, Shanshan ZHENG, et al. Advances in the research and application of neurokinin-1 receptor antagonists. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(2):91-105(2024)
洪翔宇,马俊杰,郑珊珊等.神经激肽1受体拮抗剂的研究与应用进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(02):91-105. DOI： 10.1631/jzus.B2300455.

Xiangyu HONG, Junjie MA, Shanshan ZHENG, et al. Advances in the research and application of neurokinin-1 receptor antagonists. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(2):91-105(2024) DOI： 10.1631/jzus.B2300455.

摘要

目前研究已经发现神经肽（SP）/神经激肽1受体（NK-1R）拮抗剂系统参与了包括2019冠状病毒病（COVID-19）症状在内的多种人体生理疾病。肿瘤学领域的最新研究表明：NK-1R的上调和SP/NK-1R系统的激活与多种癌症类型的进展和不良临床预后之间存在复杂的相关性，使用NK-1R拮抗剂来调节SP/NK-1R系统可成为一种潜在的广谱抗肿瘤策略。本文综述了NK-1R拮抗剂在人体生理疾病和癌症治疗中的最新应用和潜力以及相关机制，总结了改善NK-1R拮抗剂生物利用度和药效的策略（如固体分散系统、纳米化、纳米封装等），同时探讨了在放射药物治疗中，阿瑞匹坦作为放射配体受体以靶向过表达NK-1R的肿瘤疗法。此外，本文还总结了NK-1R拮抗剂与其他药物的协同效应，为NK-1R拮抗剂的创新应用提供了参考。

Abstract

Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy. This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers, as well as the underlying mechanisms. Furthermore, the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized, such as solid dispersion systems, nanonization, and nanoencapsulation. As a radiopharmaceutical therapeutic, the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors. However, combining NK-1R antagonists with other drugs can produce a synergistic effect, thereby enhancing the therapeutic effect, alleviating the symptoms, and improving patients’ quality of life in several diseases and cancers.

关键词

神经激肽1受体（NK-1R）拮抗剂阿瑞匹坦生理疾病2019冠状病毒病（COVID-19）肿瘤靶点纳米包被生物相容性放射性配体受体联合疗法

Keywords

Neurokinin-1 receptor (NK-1R) antagonistPathophysiological disorderTumor targetBioavailabilityNanoencapsulationSynergistic therapy

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Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

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