Recent advances in developing targeted protein degraders

被引：4

作者：

Cheng, Binbin ^{[1
,2
]}

Li, Hongqiao ^{[3
]}

Peng, Xiaopeng ^{[4
]}

Chen, Jianjun ^{[5
]}

Shao, Chuxiao ^{[2
]}

Kong, Zhihua ^{[6
]}

机构：

[1] Hubei Polytech Univ, Hubei Key Lab Kidney Dis Pathogenesis & Intervent, Huangshi 435003, Peoples R China

[2] Wenzhou Med Univ, Lishui Peoples Hosp, Cent Lab, Lishui Hosp, Lishui 323000, Zhejiang, Peoples R China

[3] Cent Hosp Huangshi, Huangshi 435000, Peoples R China

[4] Gannan Med Univ, Coll Pharm, Ganzhou 314000, Peoples R China

[5] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, NMPA Key Lab Res & Evaluat Drug Metab, Guangzhou 510515, Peoples R China

[6] Guangdong Prov Hosp, Integrated Tradit Chinese & Western Med, Foshan 528200, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2025年 / 284卷

基金：

中国国家自然科学基金;

关键词：

Targeted protein degradation; Small molecule ligands; PROTACs; Molecular glues; LYTACs; HyTTD; ANTIBODY-BASED PROTACS; MDM2; INHIBITORS; CANCER-THERAPY; DEGRADATION; DISCOVERY; LIGASE; ASGPR; POTENT;

D O I：

10.1016/j.ejmech.2024.117212

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Targeted protein degradation (TPD) represents a promising therapeutic approach, encompassing several innovative strategies, including but not limited to proteolysis targeting chimeras (PROTACs), molecular glues, hydrophobic tag tethering degraders (HyTTD), and lysosome-targeted chimeras (LYTACs). Central to TPD are small molecule ligands, which play a critical role in mediating the degradation of target proteins. This review summarizes the current landscape of small molecule ligands for TPD molecules. These small molecule ligands can utilize the proteasome, lysosome, autophagy, or hydrophobic-tagging system to achieve the degradation of target proteins. The article mainly focuses on introducing their design principles, application advantages, and potential limitations. A brief discussion on the development prospects and future directions of TPD technology was also provided.

引用

页数：19

共 50 条

[31] Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives [J].

Li, Jiahao ;

Gong, Chen ;

Zhou, Haiting ;

Liu, Junxia ;

Xia, Xiaohui ;

Ha, Wentao ;

Jiang, Yizhi ;

Liu, Qingxu ;

Xiong, Huihua .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (10)

[32] Applications of Bacterial Degrons and Degraders - Toward Targeted Protein Degradation in Bacteria [J].

Izert, Matylda Anna ;

Klimecka, Maria Magdalena ;

Gorna, Maria Wiktoria .

FRONTIERS IN MOLECULAR BIOSCIENCES, 2021, 8

[33] Engineered platelets as targeted protein degraders and application to breast cancer models [J].

Chen, Yu ;

Pal, Samira ;

Li, Wen ;

Liu, Fengyuan ;

Yuan, Sichen ;

Hu, Quanyin .

NATURE BIOTECHNOLOGY, 2024,

[34] Monovalent protein-degraders - Insights and future perspectives [J].

Cornella-Taracido, Ivan ;

Garcia-Echeverria, Carlos .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (12)

[35] Development of natural product-based targeted protein degraders as anticancer agents [J].

Chen, Cheng ;

Feng, Yanyan ;

Zhou, Chen ;

Liu, Zhouyan ;

Tang, Ziwei ;

Zhang, Ye ;

Li, Tong ;

Gu, Chenglei ;

Chen, Jichao .

BIOORGANIC CHEMISTRY, 2024, 153

[36] Recent Advances in Small Molecule PROTACs for the Treatment of Cancer [J].

Li, Wen ;

Elhassan, Reham M. ;

Hou, Xuben ;

Fang, Hao .

CURRENT MEDICINAL CHEMISTRY, 2021, 28 (24) :4893-4909

[37] Recent advances in the molecular targeted drugs for prostate cancer [J].

Gao, Pudong ;

Li, Tao ;

Zhang, Kuiyuan ;

Luo, Guangheng .

INTERNATIONAL UROLOGY AND NEPHROLOGY, 2023, 55 (04) :777-789

[38] Recent advances in histone deacetylase targeted cancer therapy [J].

Hoshino, Isamu ;

Matsubara, Hisahiro .

SURGERY TODAY, 2010, 40 (09) :809-815

[39] Recent advances in targeted nanomedicine as promising antitumor therapeutics [J].

Hejmady, Siddhanth ;

Pradhan, Rajesh ;

Alexander, Amit ;

Agrawal, Mukta ;

Singhvi, Gautam ;

Gorain, Bapi ;

Tiwari, Sanjay ;

Kesharwani, Prashant ;

Dubey, Sunil Kumar .

DRUG DISCOVERY TODAY, 2020, 25 (12) :2227-2244

[40] Recent advances in histone deacetylase targeted cancer therapy [J].

Isamu Hoshino ;

Hisahiro Matsubara .

Surgery Today, 2010, 40 :809-815

← 1 2 3 4 5 →