Innovative, combinatorial and high-throughput approaches to degrader synthesis

Rebecca Stevens, James D. F. Thompson, Julie C. L. Fournier, Glenn A. Burley, David J. Battersby and Afjal H. Miah

Chem. Soc. Rev., 2024, 53, 4838
DOI: 10.1039/D3CS01127E

Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design

Robert Kuchta, Christopher Heim, Alexander Herrmann, Samuel Maiwald, Yuen Lam Dora Ng, Izidor Sosič, Tim Keuler, Jan Krönke, Michael Gütschow, Marcus D. Hartmann and Christian Steinebach

RSC Chem. Biol., 2023, 4, 229
DOI: 10.1039/D2CB00223J

Targeting the deubiquitinase USP7 for degradation with PROTACs

Arunima Murgai, Izidor Sosič, Martina Gobec, Patricia Lemnitzer, Matic Proj, Sophie Wittenburg, Rabea Voget, Michael Gütschow, Jan Krönke and Christian Steinebach

Chem. Commun., 2022, 58, 8858
DOI: 10.1039/D2CC02094G

Investigating protein degradability through site-specific ubiquitin ligase recruitment

Olivia Shade, Amy Ryan, Gabriella Belsito and Alexander Deiters

RSC Chem. Biol., 2025, 6, 240
DOI: 10.1039/D4CB00273C

Rapid synthesis of pomalidomide-conjugates in minutes via temperature elevation and delayed feeding

Yingying Jiang, Hang Zhao, Lunjie Chen, Siping Wei, Jun Wang, Lin Wang and Qiang Fu

Chem. Commun., 2025, 61, 5814
DOI: 10.1039/D5CC00611B

Chemistries of bifunctional PROTAC degraders

Chaoguo Cao, Ming He, Liguo Wang, Yuna He and Yu Rao

Chem. Soc. Rev., 2022, 51, 7066
DOI: 10.1039/D2CS00220E

Utilising the intrinsic fluorescence of pomalidomide for imaging applications

Duncan K. Brownsey, Christopher J. Gafuik, Dae-Sun Kim, Leonie O’Sullivan, Evgueni Gorobets, Samuel Krukowski, Madison Turk, Craig N. Jenne, Douglas J. Mahoney and Darren J. Derksen

Chem. Commun., 2023, 59, 14532
DOI: 10.1039/D3CC04314B

Development of the first non-hydroxamate selective HDAC6 degraders

Tim Keuler, Beate König, Nico Bückreiß, Fabian B. Kraft, Philipp König, Linda Schäker-Hübner, Christian Steinebach, Gerd Bendas, Michael Gütschow and Finn K. Hansen

Chem. Commun., 2022, 58, 11087
DOI: 10.1039/D2CC03712B

Late-stage synthesis of heterobifunctional molecules for PROTAC applications via ruthenium-catalysed C‒H amidation

Daniele Antermite, Stig D. Friis, Johan R. Johansson, Okky Dwichandra Putra, Lutz Ackermann and Magnus J. Johansson

Nat Commun, 2023, 14
DOI: 10.1038/s41467-023-43789-9

NLRP3 autophagic degradation disruption in melanocytes contributes to vitiligo development

Ke Zeng, Yuqi Zhu, Zhongxin Han, Siyi Xiong, Yan Zhao, Zilong Xiao, Yingchao Xie, Shiyu Jin, Tingru Dong, Lan Lan, Weiwei Liu, Yongzhong Du, Cuiping Guan, Xiao Yu and Xiuzu Song

Cell Death Differ, 2025
DOI: 10.1038/s41418-025-01578-5

An Automated Electrochemical Flow Platform to Accelerate Library Synthesis and Reaction Optimization

Eduardo Rial‐Rodríguez, Jason D. Williams, David Cantillo, Thomas Fuchß, Alena Sommer, Hans‐Michael Eggenweiler, C. Oliver Kappe and Gabriele Laudadio

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202412045

Proteolysis‐Targeting Chimera (PROTAC): A Revolutionary Tool for Chemical Biology Research

Meichen Pan, Zhongliang Fu, Hongwei Hou, Chunrong Yang and Jinghong Li

Small Methods, 2025, 9
DOI: 10.1002/smtd.202500402

Discovery of novel protein degraders based on bioorthogonal reaction-driven intracellular self-assembly strategy

Ru Si, Huanjie Zhu, Jin Wang, Qingqing Zhang, Yanchen Li, Xiaoyan Pan and Jie Zhang

Bioorganic Chemistry, 2023, 135, 106497
DOI: 10.1016/j.bioorg.2023.106497

Reductive C(sp2)–C(sp3) Coupling Protocol to Enable Linker Exploration of Cereblon E3-Ligase BRD4 Proteolysis-Targeting Chimeras

Kaitlyn Lovato, Danielle Loskot, Christine Gelin, Lu Zhu, Charu Chaudhry, Nadeem A. Vellore, Amanda Del Rosario, Taylor Courtney, Seth Miller, Ji-Hoon Cho, Harris Bell-Temin, Jennifer D. Venable and Jean-François Brazeau

J. Med. Chem., 2025, 68, 10061
DOI: 10.1021/acs.jmedchem.4c03157

Unleashing the Power of Covalent Drugs for Protein Degradation

Meng‐Jie Fu, Hang Jin, Shao‐Peng Wang, Liang Shen, Hong‐Min Liu, Ying Liu, Yi‐Chao Zheng and Xing‐Jie Dai

Medicinal Research Reviews, 2025, 45, 1045
DOI: 10.1002/med.22101

Development of Substituted Phenyl Dihydrouracil as the Novel Achiral Cereblon Ligands for Targeted Protein Degradation

Haibo Xie, Chunrong Li, Hua Tang, Ira Tandon, Junzhuo Liao, Brett L. Roberts, Yu Zhao and Weiping Tang

J. Med. Chem., 2023, 66, 2904
DOI: 10.1021/acs.jmedchem.2c01941

Discovery of Effective Dual PROTAC Degraders for Neurodegenerative Disease-Associated Aggregates

Wentao Zhu, Wenqian Zhang, Jian Chen, Yichen Tong, Fang Xu and Jiyan Pang

J. Med. Chem., 2024, 67, 3448
DOI: 10.1021/acs.jmedchem.3c01719

A practical “preTACs-cytoblot” platform accelerates the streamlined development of PROTAC-based protein degraders

Zijian Rao, Kailin Li, Ju Hong, Danni Chen, Baoli Ding, Li Jiang, Xuxin Qi, Jiawen Hu, Bo Yang, Qiaojun He, Xiaowu Dong, Ji Cao and Cheng-Liang Zhu

European Journal of Medicinal Chemistry, 2023, 251, 115248
DOI: 10.1016/j.ejmech.2023.115248

The Discovery of a Specific CKIP-1 Ligand for the Potential Treatment of Disuse Osteoporosis

Yange Wei, Bo Wu, Mingqiu Liu and Chun-Ping Cui

IJMS, 2024, 25, 8870
DOI: 10.3390/ijms25168870

Design, synthesis and biological evaluation of novel TMPRSS2-PROTACs with florosubstituted 4-guanidino-N-phenylbenzamide derivative ligands

Hao Yang, Haoran Xu, Xinxin Lin, Zengxuan Cai, Yong Xia, Yu Wang, Zejie Chen, Koutian Zhang, Yanling Wu, Jianwei Wang, Annoor Awadasseid and Wen Zhang

Bioorganic & Medicinal Chemistry, 2024, 116, 117982
DOI: 10.1016/j.bmc.2024.117982

Facile and Practical Synthesis of Substituted Piperidine‐2,6‐Diones Under Transition‐Metal Free Condition

Yue‐Hua Liu, Zhang‐Qin Xue, Kai‐Wen Yang, Hao‐Wen Yin, Bo Yang, Rui Zhang, Hao Zhong and Zhu‐Shuang Bai

ChemistryOpen, 2025
DOI: 10.1002/open.202500067

Novel approaches to targeted protein degradation technologies in drug discovery

Yu Xue, Andrew A. Bolinger and Jia Zhou

Expert Opinion on Drug Discovery, 2023, 18, 467
DOI: 10.1080/17460441.2023.2187777

Small-Molecule Ferritin Degrader as a Pyroptosis Inducer

Yu Chen, Wen Li, Song Kwon, Yixin Wang, Zhaoting Li and Quanyin Hu

J. Am. Chem. Soc., 2023, 145, 9815
DOI: 10.1021/jacs.3c01852

Anhydrous and Stereoretentive Fluoride-Enhanced Suzuki–Miyaura Coupling of Immunomodulatory Imide Drug Derivatives

William F. Tracy, Geraint H. M. Davies, Lauren N. Grant, Jacob M. Ganley, Jesus Moreno, Emily C. Cherney and Huw M. L. Davies

J. Org. Chem., 2024, 89, 4595
DOI: 10.1021/acs.joc.3c02873

Lung‐Targeted Lipid Nanoparticle‐Delivered siUSP33 Attenuates SARS‐CoV‐2 Replication and Virulence by Promoting Envelope Degradation

Yuzheng Zhou, Yujie Liao, Lujie Fan, Xiafei Wei, Qiang Huang, Chuwei Yang, Wei Feng, Yezi Wu, Xiang Gao, Xiaotong Shen, Jian Zhou, Zanxian Xia and Zheng Zhang

Advanced Science, 2024, 11
DOI: 10.1002/advs.202406211

Rational Design of Dual Degraders by Incorporating Molecular Glue Structural Features into PROTAC Degraders

Bowen Zhang, Shan Gao, Tingting Wu, Yan Ma, Senbiao Fang, Mengyan Rong, Wenrui Jia, Sai Zhang, Hui Hou, Xiao Wang, Siqi Zhang and Chong Qin

J. Med. Chem., 2025, 68, 10268
DOI: 10.1021/acs.jmedchem.5c00443

Diversity Synthesis Using Glutarimides as Rhodium Carbene Precursors in Enantioselective C–H Functionalization and Cyclopropanation

William F. Tracy, Jack C. Sharland, Duc Ly, Geraint H. M. Davies, Djamaladdin G. Musaev, Hua Fang, Jesus Moreno, Emily C. Cherney and Huw M. L. Davies

J. Am. Chem. Soc., 2025, 147, 11336
DOI: 10.1021/jacs.5c00568

E3Docker: a docking server for potential E3 binder discovery

Kejia Yan, Wangqiu He, Mingwei Pang, Xufeng Lu, Zhou Chen, Lianhua Piao, Han Zhang, Yu Wang, Shan Chang and Ren Kong

Nucleic Acids Research, 2025, 53, W266
DOI: 10.1093/nar/gkaf391

Novel Design Strategies to Enhance the Efficiency of Proteolysis Targeting Chimeras

Chunlong Zhao and Frank J. Dekker

ACS Pharmacol. Transl. Sci., 2022, 5, 710
DOI: 10.1021/acsptsci.2c00089

Advances in DNA-based proteolysis-targeting chimeras technology: Novel strategies for targeting previously undruggable proteins in cancer therapy

Min Hou, Mingda Li, Yulin Li, Xiaobo Wu, Die Long, Di Sun and Jincheng Zeng

Bioorganic & Medicinal Chemistry, 2025, 129, 118297
DOI: 10.1016/j.bmc.2025.118297

Current advances of small molecule E3 ligands for proteolysis-targeting chimeras design

Dazhao Mi, Yuzhan Li, Haijun Gu, Yan Li and Yihua Chen

European Journal of Medicinal Chemistry, 2023, 256, 115444
DOI: 10.1016/j.ejmech.2023.115444

LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer

Yingming Jiang, Yanchun Feng, Jintuan Huang, Zhenze Huang, Rongchang Tan, Tuoyang Li, Zijian Chen, Xiaocheng Tang, Jun Qiu, Chujun Li, Hao Chen and Zuli Yang

J Transl Med, 2023, 21
DOI: 10.1186/s12967-023-04401-2

Histone Deacetylase 3‐Directed PROTACs Have Anti‐inflammatory Potential by Blocking Polarization of M0‐like into M1‐like Macrophages

Chunlong Zhao, Shipeng Chen, Deng Chen, Clàudia Río‐Bergé, Jianqiu Zhang, Petra E. Van Der Wouden, Toos Daemen and Frank J. Dekker

Angewandte Chemie, 2023, 135
DOI: 10.1002/ange.202310059

Discovery of selective platelet-derived growth factor receptor-beta (PDGFR-β) bifunctional small-molecule degraders

Ru Si, Nanxin Liu, Jin Wang, Qingqing Zhang, Yanchen Li, Xiaoyan Pan and Jie Zhang

Bioorganic & Medicinal Chemistry, 2023, 77, 117115
DOI: 10.1016/j.bmc.2022.117115

CircRNF10 triggers a positive feedback loop to facilitate progression of glioblastoma via redeploying the ferroptosis defense in GSCs

Chengbin Wang, Minjie Zhang, Yingliang Liu, Daming Cui, Liang Gao and Yang Jiang

J Exp Clin Cancer Res, 2023, 42
DOI: 10.1186/s13046-023-02816-9

Journey of Von Hippel-Lindau (VHL) E3 ligase in PROTACs design: From VHL ligands to VHL-based degraders

Nisha Setia, Haider Thaer Abdulhameed Almuqdadi and Mohammad Abid

European Journal of Medicinal Chemistry, 2024, 265, 116041
DOI: 10.1016/j.ejmech.2023.116041

Formation of C(sp2)–C(sp3) Bonds Instead of Amide C–N Bonds from Carboxylic Acid and Amine Substrate Pools by Decarbonylative Cross-Electrophile Coupling

Jiang Wang, Lauren E. Ehehalt, Zhidao Huang, Omar M. Beleh, Ilia A. Guzei and Daniel J. Weix

J. Am. Chem. Soc., 2023, 145, 9951
DOI: 10.1021/jacs.2c11552

Leveraging Ligand Affinity and Properties: Discovery of Novel Benzamide-Type Cereblon Binders for the Design of PROTACs

Christian Steinebach, Aleša Bricelj, Arunima Murgai, Izidor Sosič, Luca Bischof, Yuen Lam Dora Ng, Christopher Heim, Samuel Maiwald, Matic Proj, Rabea Voget, Felix Feller, Janez Košmrlj, Valeriia Sapozhnikova, Annika Schmidt, Maximilian Rudolf Zuleeg, Patricia Lemnitzer, Philipp Mertins, Finn K. Hansen, Michael Gütschow, Jan Krönke and Marcus D. Hartmann

J. Med. Chem., 2023, 66, 14513
DOI: 10.1021/acs.jmedchem.3c00851

A beginner’s guide to current synthetic linker strategies towards VHL-recruiting PROTACs

Nikol A. Zografou-Barredo, Alex J. Hallatt, Jennyfer Goujon-Ricci and Céline Cano

Bioorganic & Medicinal Chemistry, 2023, 88-89, 117334
DOI: 10.1016/j.bmc.2023.117334

Fangchinoline suppresses hepatocellular carcinoma by regulating ROS accumulation via the TRIM7/Nrf2 signaling pathway

Yange Liu, Yawen Wang, Juan Wang, Xingxing Wang, Luoting Chen, Tianyu Han, Hang Lian, Mingxi Gan and Jianbin Wang

Phytomedicine, 2024, 135, 156143
DOI: 10.1016/j.phymed.2024.156143

Targeting androgen receptor degradation with PROTACs from bench to bedside

Xiaojuan Jia and Xin Han

Biomedicine & Pharmacotherapy, 2023, 158, 114112
DOI: 10.1016/j.biopha.2022.114112

E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat

Jian Yu, Xuejiang Gu, Yingying Guo, Mingyuan Gao, Shimiao Cheng, Meiyao Meng, Xiangdi Cui, Zhe Zhang, Wenxiu Guo, Dandan Yan, Maozheng Sheng, Linhui Zhai, Jing Ji, Xinhui Ma, Yu Li, Yuxiang Cao, Xia Wu, Jiejie Zhao, Yepeng Hu, Minjia Tan, Yan Lu, Lingyan Xu, Bin Liu, Cheng Hu and Xinran Ma

EMBO Rep, 2025, 26, 748
DOI: 10.1038/s44319-024-00337-w

Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs

André T. S. Vicente, Sara P. S. P. Moura and Jorge A. R. Salvador

Commun Chem, 2025, 8
DOI: 10.1038/s42004-025-01598-9

Design, synthesis, and biological activity of novel pomalidomide linked with diphenylcarbamide derivatives

Bin Sun, Xiaofei Liu, Tao Ji, Xiaoguang Zhan, Longfei Mao, Peng Deng and Lin Shi

Heterocyclic Communications, 2022, 28, 174
DOI: 10.1515/hc-2022-0155

Protein degradation: expanding the toolbox to restrain cancer drug resistance

Hui Ming, Bowen Li, Jingwen Jiang, Siyuan Qin, Edouard C. Nice, Weifeng He, Tingyuan Lang and Canhua Huang

J Hematol Oncol, 2023, 16
DOI: 10.1186/s13045-023-01398-5

What influences the activity of Degrader−Antibody conjugates (DACs)

Yaolin Guo, Xiaoxue Li, Yang Xie and Yuxi Wang

European Journal of Medicinal Chemistry, 2024, 268, 116216
DOI: 10.1016/j.ejmech.2024.116216

Asymmetric Dirhodium-Catalyzed Modification of Immunomodulatory Imide Drugs and Their Biological Assessment

William F. Tracy, Geraint H. M. Davies, Lei Jia, Ethan D. Evans, Zhenghang Sun, Jennifer Buenviaje, Gody Khambatta, Shan Yu, Lihong Shi, Veerabahu Shanmugasundaram, Jesus Moreno, Emily C. Cherney and Huw M. L. Davies

ACS Med. Chem. Lett., 2024, 15, 1575
DOI: 10.1021/acsmedchemlett.4c00297

Tactics and Strategies for the Synthesis of Cereblon Ligands

Elisia Villemure, Yong Wang, Yuebiao Zhou, Alice R. Wong and Christian Nilewski

Synthesis, 2024, 56, 3543
DOI: 10.1055/s-0043-1775385

A region-confined PROTAC nanoplatform for spatiotemporally tunable protein degradation and enhanced cancer therapy

Jing Gao, Xingyu Jiang, Shumin Lei, Wenhao Cheng, Yi Lai, Min Li, Lei Yang, Peifeng Liu, Xiao-hua Chen, Min Huang, Haijun Yu, Huixiong Xu and Zhiai Xu

Nat Commun, 2024, 15
DOI: 10.1038/s41467-024-50735-w

Covalent Bifunctional Molecules (CBMs): Achievements and Challenges

Yuting Xin, Fangsu Chen, Qidong You, Lei Wang and Qiuyue Zhang

Medicinal Research Reviews, 2025
DOI: 10.1002/med.70011

Accelerating PROTACs Discovery Through a Direct‐to‐Biology Platform Enabled by Modular Photoclick Chemistry

Ke‐Nian Yan, Yong‐Qiang Nie, Jia‐Yu Wang, Guang‐Liang Yin, Qia Liu, Hao Hu, Xiaoxia Sun and Xiao‐Hua Chen

Advanced Science, 2024, 11
DOI: 10.1002/advs.202400594

Development of the first geldanamycin-based HSP90 degraders

Silas Wurnig, Melina Vogt, Julian Hogenkamp, Niklas Dienstbier, Arndt Borkhardt, Sanil Bhatia and Finn K. Hansen

Front. Chem., 2023, 11
DOI: 10.3389/fchem.2023.1219883

Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer

Laura Rinaldi, Francesco Chiuso, Emanuela Senatore, Domenica Borzacchiello, Luca Lignitto, Rosa Iannucci, Rossella Delle Donne, Mariano Fuggi, Carla Reale, Filomena Russo, Nicola Antonino Russo, Giorgio Giurato, Francesca Rizzo, Assunta Sellitto, Michele Santangelo, Davide De Biase, Orlando Paciello, Chiara D’Ambrosio, Stefano Amente, Corrado Garbi, Emiliano Dalla, Andrea Scaloni, Alessandro Weisz, Concetta Ambrosino, Luigi Insabato and Antonio Feliciello

Commun Biol, 2024, 7
DOI: 10.1038/s42003-024-05823-4

MyD88 protein destabilization mitigates NF-κB-dependent protection against macrophage apoptosis

Duško Lainšček, Simon Horvat, Klemen Dolinar, Filip Ivanovski, Rok Romih, Sergej Pirkmajer, Roman Jerala and Mateja Manček-Keber

Cell Commun Signal, 2024, 22
DOI: 10.1186/s12964-024-01930-1

Chemically induced degradation of PRC2 complex by EZH2-Targeted PROTACs via a Ubiquitin-Proteasome pathway

Mingwei Fu, Yuanjiang Wang, Min Ge, Chunchen Hu, Ya Xiao, Yan Ma and Shaohua Gou

Bioorganic & Medicinal Chemistry Letters, 2024, 113, 129968
DOI: 10.1016/j.bmcl.2024.129968

Advances in designing ternary complexes: Integrating in-silico and biochemical methods for PROTAC optimisation in target protein degradation

Shareef Shaik, Prasanna Kumar Reddy Gayam, Manish Chaudhary, Gurvinder Singh and Aravinda Pai

Bioorganic Chemistry, 2024, 153, 107868
DOI: 10.1016/j.bioorg.2024.107868

Modulating the Potency of BRD4 PROTACs at the Systems Level with Amine-Acid Coupling Reactions

Andrew McGrath, Haiyan Huang, Jean-Francois Brazeau, Zirong Zhang, Christopher O. Audu, Nadeem A. Vellore, Lu Zhu, Zhicai Shi, Jennifer D. Venable, Christine F. Gelin and Tim Cernak

J. Med. Chem., 2025, 68, 405
DOI: 10.1021/acs.jmedchem.4c02047

Antiviral PROTACs: Opportunity borne with challenge

Jinsen Liang, Yihe Wu, Ke Lan, Chune Dong, Shuwen Wu, Shu Li and Hai-Bing Zhou

Cell Insight, 2023, 2, 100092
DOI: 10.1016/j.cellin.2023.100092

Histone Deacetylase 3‐Directed PROTACs Have Anti‐inflammatory Potential by Blocking Polarization of M0‐like into M1‐like Macrophages

Chunlong Zhao, Shipeng Chen, Deng Chen, Clàudia Río‐Bergé, Jianqiu Zhang, Petra E. Van Der Wouden, Toos Daemen and Frank J. Dekker

Angew Chem Int Ed, 2023, 62
DOI: 10.1002/anie.202310059

The E3 ligase NEURL3 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma by promoting vimentin degradation

Shi-Qing Zhou, Ping Feng, Ming-Liang Ye, Sheng-Yan Huang, Shi-Wei He, Xun-Hua Zhu, Jun Chen, Qun Zhang and Ying-Qing Li

J Exp Clin Cancer Res, 2024, 43
DOI: 10.1186/s13046-024-02945-9

TRIM21-mediated Sohlh2 ubiquitination suppresses M2 macrophage polarization and progression of triple-negative breast cancer

Ruihong Zhang, Ying Shen, Qi Zhang, Xiaoning Feng, Xuyue Liu, Xiaoning Huo, Jinhao Sun and Jing Hao

Cell Death Dis, 2023, 14
DOI: 10.1038/s41419-023-06383-x

A Modular Chemistry Platform for the Development of a Cereblon E3 Ligase‐Based Partial PROTAC Library

Chelsi M. Almodóvar‐Rivera, Zhen Zhang, Jingyao Li, Haibo Xie, Yu Zhao, Le Guo, Marissa G. Mannhardt and Weiping Tang

ChemBioChem, 2023, 24
DOI: 10.1002/cbic.202300482

Solid‐Phase Synthesis of PROTACs and SNIPERs on Backbone Amide Linked (BAL) Resin

Liam Thomas Hales and Philip Evan Thompson

Chemistry A European J, 2023, 29
DOI: 10.1002/chem.202301975

Computational investigations of indanedione and indanone derivatives in drug discovery: Indanone derivatives inhibits cereblon, an E3 ubiquitin ligase component

Upendra Nayek, Syed Ibrahim Basheer Ahamed, Ummul Halilunnisa Mansoor Hussain, Mazhuvancherry Kesavan Unnikrishnan and Abdul Ajees Abdul Salam

Computational Biology and Chemistry, 2022, 101, 107776
DOI: 10.1016/j.compbiolchem.2022.107776

Distal C(sp3)-H Amidation via Ind*RhIII Catalyzed Nitrene Transfer

Hannah J. Ross, Yihui Yu, Liselle Atkin, Milad Ghorbani, Kelly Mint, Nicole Warne, Kristian Kempe and Daniel L. Priebbenow

J. Am. Chem. Soc., 2025, 147, 24734
DOI: 10.1021/jacs.5c06232

Redox regulation: mechanisms, biology and therapeutic targets in diseases

Bowen Li, Hui Ming, Siyuan Qin, Edouard C. Nice, Jingsi Dong, Zhongyan Du and Canhua Huang

Sig Transduct Target Ther, 2025, 10
DOI: 10.1038/s41392-024-02095-6

Targeting focal adhesion kinase (FAK) for cancer therapy: FAK inhibitors, FAK-based dual-target inhibitors and PROTAC degraders

Ming Yang, Hua Xiang and Guoshun Luo

Biochemical Pharmacology, 2024, 224, 116246
DOI: 10.1016/j.bcp.2024.116246

Expanding the Structural Diversity at the Phenylene Core of Ligands for the von Hippel–Lindau E3 Ubiquitin Ligase: Development of Highly Potent Hypoxia-Inducible Factor-1α Stabilizers

Lan Phuong Vu, Claudia J. Diehl, Ryan Casement, Adam G. Bond, Christian Steinebach, Nika Strašek, Aleša Bricelj, Andrej Perdih, Gregor Schnakenburg, Izidor Sosič, Alessio Ciulli and Michael Gütschow

J. Med. Chem., 2023, 66, 12776
DOI: 10.1021/acs.jmedchem.3c00434

An Automated Electrochemical Flow Platform to Accelerate Library Synthesis and Reaction Optimization

Eduardo Rial‐Rodríguez, Jason D. Williams, David Cantillo, Thomas Fuchß, Alena Sommer, Hans‐Michael Eggenweiler, C. Oliver Kappe and Gabriele Laudadio

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202412045

Strategic advancement of E3 ubiquitin ligase in the management of hepatocellular carcinoma

Yangyang Miao, Shunyi Wang, Jiahao Zhang, Huanxiang Liu, Chi Zhang, Shengjie Jin and Dousheng Bai

Med Oncol, 2024, 41
DOI: 10.1007/s12032-024-02411-8

Potential of the nanoplatform and PROTAC interface to achieve targeted protein degradation through the Ubiquitin–Proteasome system

Hanshu Xie and Chao Zhang

European Journal of Medicinal Chemistry, 2024, 267, 116168
DOI: 10.1016/j.ejmech.2024.116168

The Peptide PROTAC Modality: A New Strategy for Drug Discovery

Youmin Zhu, Yu Dai and Yuncai Tian

MedComm, 2025, 6
DOI: 10.1002/mco2.70133

Photoredox Csp3−Csp2 Reductive Cross‐Couplings of Cereblon Ligands for PROTAC Linker Exploration in Batch and Flow

Alexander Steiner, Johannes Krieger, Reinaldo Jones, Dietrich Böse, Yanping Wang, Hans‐Michael Eggenweiler, Jason D. Williams and C. Oliver Kappe

ChemCatChem, 2022, 14
DOI: 10.1002/cctc.202201184

CRBN‐PROTACs in Cancer Therapy: From Mechanistic Insights to Clinical Applications

Riya Thapa, Asif Ahmad Bhat, Gaurav Gupta, S. Renuka Jyothi, Irwanjot Kaur, Sachin Kumar, Naveen Sharma, G. V. Siva Prasad, Atreyi Pramanik and Haider Ali

Chem Biol Drug Des, 2024, 104
DOI: 10.1111/cbdd.70009

PROTACs: A novel strategy for cancer drug discovery and development

Xin Han and Yi Sun

MedComm, 2023, 4
DOI: 10.1002/mco2.290

Exploration of Hydrazide-Based HDAC8 PROTACs for the Treatment of Hematological Malignancies and Solid Tumors

Chunlong Zhao, Jianqiu Zhang, Hangyu Zhou, Rita Setroikromo, Gerrit J. Poelarends and Frank J. Dekker

J. Med. Chem., 2024, 67, 14016
DOI: 10.1021/acs.jmedchem.4c00836

Identification and structural basis of C-terminal cyclic imides as natural degrons for cereblon

Christopher Heim, Anna-Katharina Spring, Sören Kirchgäßner, Dirk Schwarzer and Marcus D. Hartmann

Biochemical and Biophysical Research Communications, 2022, 637, 66
DOI: 10.1016/j.bbrc.2022.11.001

Cereblon neo-substrate binding mimics the recognition of the cyclic imide degron

Christopher Heim, Anna-Katharina Spring, Sören Kirchgäßner, Dirk Schwarzer and Marcus D. Hartmann

Biochemical and Biophysical Research Communications, 2023, 646, 30
DOI: 10.1016/j.bbrc.2023.01.051

Small-Molecule PROTACs for Cancer Immunotherapy

Zefan Liu, Yajun Zhang, Yucheng Xiang and Xin Kang

Molecules, 2022, 27, 5439
DOI: 10.3390/molecules27175439

Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery

Yilin Liu, Xiao Zhang, Xiaoyuan Chen and Fuwu Zhang

Biomaterials, 2026, 325, 123621
DOI: 10.1016/j.biomaterials.2025.123621

Drugging the undruggable: Chemical and biological insights into molecular glues in the pipeline

Kamel Metwally, Galal Yahya and Nader E. Abo-Dya

European Journal of Medicinal Chemistry, 2025, 300, 118132
DOI: 10.1016/j.ejmech.2025.118132

Synergistic induction of ferroptosis by targeting HERC1-NCOA4 axis to enhance the photodynamic sensitivity of osteosarcoma

Ye Zhang, Yuxing Chen, Hai Mou, Qiu Huang, Changchun Jian, Yong Tao, Fuqiang Tan and Yunsheng Ou

Redox Biology, 2024, 76, 103328
DOI: 10.1016/j.redox.2024.103328

Discovery of highly potent HDAC8 PROTACs with anti-tumor activity

Chunlong Zhao, Deng Chen, Fengzhi Suo, Rita Setroikromo, Wim J. Quax and Frank J. Dekker

Bioorganic Chemistry, 2023, 136, 106546
DOI: 10.1016/j.bioorg.2023.106546

Computational methods and key considerations for in silico design of proteolysis targeting chimera (PROTACs)

Amr Abbas and Fei Ye

International Journal of Biological Macromolecules, 2024, 277, 134293
DOI: 10.1016/j.ijbiomac.2024.134293

A Cell-Permeant Nanobody-Based Degrader That Induces Fetal Hemoglobin

Fangfang Shen, Ge Zheng, Mekedlawit Setegne, Karin Tenglin, Manizheh Izadi, Henry Xie, Liting Zhai, Stuart H. Orkin and Laura M. K. Dassama

ACS Cent. Sci., 2022, 8, 1695
DOI: 10.1021/acscentsci.2c00998

The role of UBR5 in tumor proliferation and oncotherapy

Bin Hu and Shiyuan Chen

Gene, 2024, 906, 148258
DOI: 10.1016/j.gene.2024.148258

Small molecule inhibitors targeting the cancers

Gui‐Hong Liu, Tao Chen, Xin Zhang, Xue‐Lei Ma and Hua‐Shan Shi

MedComm, 2022, 3
DOI: 10.1002/mco2.181

FBXO11 amplifies type I interferon signaling to exert antiviral effects by facilitating the assemble of TRAF3–TBK1–IRF3 complex

Long Gao, Yufeng Gao, Kexing Han, Zining Wang, Fang Meng, Jiaying Liu, Xin Zhao, Yun Shao, Jiapei Shen, Weijie Sun, Yanyan Liu, Honghai Xu, Xiaohong Du, Jiabin Li and Frank Xiao‐Feng Qin

Journal of Medical Virology, 2023, 95
DOI: 10.1002/jmv.28655

Discovery of NAFLD-Improving Agents by Promoting the Degradation of Keap1

Mingming Qi, Hui Zhong, Zhaoyan Cheng, Shujie Chen, Han Xiao, Jing Shang, Li Chen and Jianbo Sun

J. Med. Chem., 2023, 66, 9184
DOI: 10.1021/acs.jmedchem.3c00822

Advancing target validation with PROTAC technology

M. Leora Spitz, Aseel Kashkush and Raphael I. Benhamou

Expert Opinion on Drug Discovery, 2025, 20, 551
DOI: 10.1080/17460441.2025.2490248

Role and therapeutic potential of E3s in the tumor microenvironment of hepatocellular carcinoma

Hailin Wang, Qiang Li, Qinqin Tang, Gang Shi, Guo Wu, Xingbo Mao, Changkang Wu, Lixin Zhang, Jie Liu, Jingdong Li and Bo Li

Front. Immunol., 2024, 15
DOI: 10.3389/fimmu.2024.1483721

Recent breakthroughs in innovative elements, multidimensional enhancements, derived technologies, and novel applications of PROTACs

Si-Han Zhang, Na Zeng, Jin-Zhou Xu, Chen-Qian Liu, Meng-Yao Xu, Jian-Xuan Sun, Ye An, Xing-Yu Zhong, Lin-Tao Miao, Shao-Gang Wang and Qi-Dong Xia

Biomedicine & Pharmacotherapy, 2024, 180, 117584
DOI: 10.1016/j.biopha.2024.117584

Synthesis of selective BCL-XL PROTAC and potent antitumor activity in glioblastoma

Meichen Liu, Biao Sun, Rui Niu, Yue Zhang, Xinyu Li, Jiefei Wang, Xin Wang and Jinlong Yin

Cell Reports Physical Science, 2025, 6, 102593
DOI: 10.1016/j.xcrp.2025.102593

DeepPSA: A Geometric Deep Learning Model for PROTAC Synthetic Accessibility Prediction

Ran Zhang, Shihang Wang, Lin Wang, Siyuan Tian, Yilin Tang and Fang Bai

J. Chem. Inf. Model., 2025, 65, 6861
DOI: 10.1021/acs.jcim.5c00366

An updated review on the role of small molecules in mediating protein degradation

Zumei Wu, Yulong Li, Jinyun Dong and Jiang-Jiang Qin

European Journal of Medicinal Chemistry, 2025, 287, 117370
DOI: 10.1016/j.ejmech.2025.117370

PROTAC-Mediated GSPT1 Degradation Impairs the Expression of Fusion Genes in Acute Myeloid Leukemia

Alicia Perzolli, Christian Steinebach, Jan Krönke, Michael Gütschow, C. Michel Zwaan, Farnaz Barneh and Olaf Heidenreich

Cancers, 2025, 17, 211
DOI: 10.3390/cancers17020211

Enhancing Solubility in VHL-Based PROTACs: Optimized USP7 Degraders for Improved Developability

Sophie Wittenburg, Maximilian R. Zuleeg, Kirsten Peter, Patricia Lemnitzer, Rabea Voget, Aleša Bricelj, Martina Gobec, Nele Dierlamm, Michael B. Braun, Thomas M. Geiger, Christopher Heim, Alicia Stakemeier, Karl G. Wagner, Radosław P. Nowak, Marcus D. Hartmann, Izidor Sosič, Michael Gütschow, Jan Krönke and Christian Steinebach

J. Med. Chem., 2025, 68, 15711
DOI: 10.1021/acs.jmedchem.5c00718