Development of natural product-based targeted protein degraders as anticancer agents

被引：5

作者：

Chen, Cheng ^{[1
]}

Feng, Yanyan ^{[1
]}

Zhou, Chen ^{[3
]}

Liu, Zhouyan ^{[1
]}

Tang, Ziwei ^{[1
]}

Zhang, Ye ^{[2
]}

Li, Tong ^{[1
]}

Gu, Chenglei ^{[1
]}

Chen, Jichao ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China

[2] Changzhou Univ, Sch Petrochem Engn, Changzhou 213164, Peoples R China

[3] Univ Florida, Coll Pharm, Dept Med Chem, Gainesville, FL 32610 USA

来源：

BIOORGANIC CHEMISTRY | 2024年 / 153卷

基金：

中国国家自然科学基金;

关键词：

Natural product; PROTAC; Molecular glue; Hydrophobic tagging; Anticancer; PSEUDOLARIC ACID B; CELL-CYCLE; QUALITY-CONTROL; ANTITUMOR-ACTIVITY; SMALL MOLECULES; DRUG DISCOVERY; DEGRADATION; CANCER; PROTAC; STAT3;

D O I：

10.1016/j.bioorg.2024.107772

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Targeted protein degradation (TPD) has emerged as a powerful approach for eliminating cancer-causing proteins through an "event-driven" pharmacological mode. Proteolysis-targeting chimeras (PROTACs), molecular glues (MGs), and hydrophobic tagging (HyTing) have evolved into three major classes of TPD technologies. Natural products (NPs) are a primary source of anticancer drugs and have played important roles in the development of TPD technology. NPs potentially expand the toolbox of TPD by providing a variety of E3 ligase ligands, protein of interest (POI) warheads, and hydrophobic tags (HyTs). As a promising direction in the TPD field, NP-based degraders have shown great potential for anticancer therapy. In this review, we summarize recent advances in the development of NP-based degraders (PROTACs, MGs and HyTing) with anticancer applications. Moreover, we put forward the challenges while presenting potential opportunities for the advancement of future targeted protein degraders derived from NPs.

引用

页数：18

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