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乳腺癌治疗中的蛋白酶靶向嵌合体(PROTACs)

Proteolysis Targeting Chimeras (PROTACs) in Breast Cancer Therapy.

作者信息

Jin Yerim, Lee Yeongju

机构信息

Department of Chemistry, Pusan National University, Busan, 46241, Korea.

出版信息

ChemMedChem. 2024 Dec 2;19(23):e202400267. doi: 10.1002/cmdc.202400267. Epub 2024 Oct 15.

Abstract

Breast cancer (BC) accounts for 30 % of cancer cases among women cancer patients globally, indicating the urgent need for the development of selective therapies targeting BCs. Recently, proteolysis-targeting chimera (PROTAC) has emerged as a promising strategy to target breast cancer. PROTAC is a chimeric molecule consisting of a target protein ligand, an E3 ligase ligand, and conjugating linkers, enabling it to facilitate the degradation of desired target proteins by recruiting E3 ligase in close proximity. Due to the catalytic behavior and direct degradation of BC-causing proteins, PROTAC could achieve high drug efficacy with low doses, drawing great attention for its potential as therapeutics. This review provides cases of the currently developed PROTACs targeting BCs depending on the type of BCs, limitations, and future perspectives of PROTAC in targeting BCs.

摘要

乳腺癌(BC)在全球女性癌症患者中占癌症病例的30%,这表明迫切需要开发针对乳腺癌的选择性疗法。最近,蛋白酶靶向嵌合体(PROTAC)已成为一种有前景的靶向乳腺癌的策略。PROTAC是一种嵌合分子,由靶蛋白配体、E3连接酶配体和连接接头组成,使其能够通过在附近招募E3连接酶来促进所需靶蛋白的降解。由于PROTAC对导致乳腺癌的蛋白质具有催化作用并能直接降解,因此可以低剂量实现高药物疗效,其作为治疗药物的潜力备受关注。本综述根据乳腺癌的类型介绍了目前开发的靶向乳腺癌的PROTAC案例、局限性以及PROTAC在靶向乳腺癌方面的未来前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d6e/11617661/873e38de86db/CMDC-19-e202400267-g010.jpg

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