治疗转移性激素敏感性前列腺癌的第2代雄激素受体拮抗剂瑞维鲁胺  

Revelutamide,a second-generation androgen receptor antagonist for the treatment of metastatic hormone-sensitive prostate cancer

作　　者：崔英杰 张桂芳 CUI Ying-jie;ZHANG Gui-fang(Department of Pharmacy,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,China)

机构地区：[1]山东第一医科大学附属省立医院药学部,济南250021

出　　处：《中国新药杂志》2024年第20期2109-2113,共5页Chinese Journal of New Drugs

基　　金：山东省自然科学基金资助青年项目(ZR2021QH303)。

摘　　要：瑞维鲁胺是我国自主研发的一种新型第2代雄激素受体(androgen receptor,AR)拮抗剂,通过三重强效抑制机制,达到抑制AR信号通路活化的目的,从而有效抑制前列腺癌细胞增殖。瑞维鲁胺与AR的配体结合域结合,竞争性抑制雄激素与AR结合,阻止雄激素诱导的AR活化,抑制AR核易位。瑞维鲁胺通过与DNA结合,降低AR介导的基因转录,抑制调节前列腺癌细胞增殖的基因表达。此外,瑞维鲁胺引入了双羟基,增加亲水性,水溶解度较同类产品恩杂鲁胺和阿帕他胺增加近20倍,更不易穿过血脑屏障,导致发生癫痫和乏力的风险降低。2022年6月,瑞维鲁胺在我国被批准用于治疗高肿瘤负担的转移性激素敏感性前列腺癌(metastatic hormone-sensitive prostate cancer,mHSPC)患者。本文主要对瑞维鲁胺的作用机制、药动学、安全性研究及临床应用疗效评价进行综述,旨在为新药研发及瑞维鲁胺临床应用提供理论参考。Revelutamide is a new type of second-generation androgen receptor(AR)antagonist independently developed in China,which can inhibit the activation of AR signaling pathway through a triple potent inhibition mechanism,thus effectively inhibiting the proliferation of prostate cancer cells.Revelutamide binds to the ligand-binding domain of AR,competitively inhibits the binding of androgen to AR,prevents androgen-induced AR activation,and inhibits AR nuclear translocation.It also inhibits the expression of genes that regulate prostate cancer cell proliferation by binding to DNA and reduces AR-mediated gene transcription.In addition,revelutamide introduces a double hydroxyl group,increasing its water solubility by nearly 20-fold compared to its counterparts enzalutamide and apalutamide,which is less likely to cross the blood-brain barrier,resulting in a reduced risk of seizures and lethargy.In June 2022,revilutamide was approved in China for the treatment of patients with metastatic hormone-sensitive prostate cancer(mHSPC)with high tumor burden.This article mainly reviews the mechanism of action,pharmacokinetics,safety and clinical efficacy evaluations of revirutamide,aiming to provide theoretical references for new drug development and clinical application of revirutamide.

关 键 词：瑞维鲁胺 雄激素受体拮抗剂 前列腺癌 

分 类 号：R971[医药卫生—药品]