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天然化合物在葡萄膜黑色素瘤药物研发中的应用。

The application of natural compounds in uveal melanoma drug discovery.

机构信息

Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.

出版信息

J Pharm Pharmacol. 2022 May 20;74(5):660-680. doi: 10.1093/jpp/rgac009.

Abstract

OBJECTIVES

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. UM has a poor overall prognosis and ~50% of patients progress to metastatic disease that has a median survival of 5.2 months. There are currently no proven pharmacological treatments for primary or metastatic UM. Research efforts continue to seek new agents. Many natural compounds have shown promising anti-UM activity in in-vitro and/or in-vivo studies. This review summarises the current findings for natural compounds that may be potentially useful in treating UM.

KEY FINDINGS

Literature suggests that natural compounds, such as pristimerin, picropodophyllin, oridonin, zeaxanthin, withaferin and FR-900359, may be promising candidate compounds to treat UM. Most of these compounds have demonstrated satisfactory efficacy in inhibiting in-vitro UM cell growth.

SUMMARY

The evidence regarding the anti-UM effects of natural compounds is mainly limited to in-vitro studies; to date, only a small number of these agents have been evaluated in vivo. The molecular mechanisms underpinning the anti-UM properties of these compounds remain largely undefined. Further studies are required to evaluate the in-vivo anticancer activity, appropriate dosage regimen and safety of natural compounds that could be developed for use in UM.

摘要

目的

葡萄膜黑色素瘤(UM)是成年人中最常见的原发性眼内肿瘤。UM 的总体预后较差,约有 50%的患者进展为转移性疾病,中位生存时间为 5.2 个月。目前,原发性或转移性 UM 没有经过证实的药物治疗方法。研究工作仍在继续寻找新的药物。许多天然化合物在体外和/或体内研究中表现出有希望的抗 UM 活性。这篇综述总结了可能对治疗 UM 有用的天然化合物的最新发现。

主要发现

文献表明,天然化合物,如普瑞美灵、苦鬼臼毒素、冬凌草甲素、玉米黄质、醉茄素和 FR-900359,可能是治疗 UM 的有前途的候选化合物。这些化合物中的大多数在抑制体外 UM 细胞生长方面表现出令人满意的疗效。

总结

关于天然化合物抗 UM 作用的证据主要限于体外研究;迄今为止,这些药物中只有少数在体内进行了评估。这些化合物抗 UM 特性的分子机制在很大程度上尚未确定。需要进一步研究评估可用于 UM 的天然化合物的体内抗癌活性、适当的剂量方案和安全性,以便开发利用。

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