Discovery of small molecule ligands for the von Hippel-Lindau (VHL) E3 ligase and their use as inhibitors and PROTAC degraders

Claudia J. Diehl and Alessio Ciulli

Chem. Soc. Rev., 2022, 51, 8216
DOI: 10.1039/D2CS00387B

Cereblon covalent modulation through structure-based design of histidine targeting chemical probes

Justin T. Cruite, Geoffrey P. Dann, Jianwei Che, Katherine A. Donovan, Silas Ferrao, Scott B. Ficarro, Eric S. Fischer, Nathanael S. Gray, Fidel Huerta, Nikki R. Kong, Hu Liu, Jarrod A. Marto, Rebecca J. Metivier, Radosław P. Nowak, Breanna L. Zerfas and Lyn H. Jones

RSC Chem. Biol., 2022, 3, 1105
DOI: 10.1039/D2CB00078D

Covalent drugs targeting histidine – an unexploited opportunity?

Jianwei Che and Lyn H. Jones

RSC Med. Chem., 2022, 13, 1121
DOI: 10.1039/D2MD00258B

Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis

Jianyu Yan, Tianyu Wang, Ruizhi Yu, Lijuan Xu, Hongming Shao, Tengfei Li, Zhe Wang, Xudong Cha, Zhenyuan Miao, Chengguo Xing, Ke Xu, Huanhai Liu and Chunlin Zhuang

Acta Pharmaceutica Sinica B, 2025, 15, 4137
DOI: 10.1016/j.apsb.2025.05.025

A degron-mimicking molecular glue drives CRBN homo-dimerization and degradation

Gerasimos Langousis, Pablo Gainza, Moritz Hunkeler, Despoina Kapsitidou, Etienne J. Donckele, Stefano Annunziato, Lars Wiedmer, Katherine F. M. Jones, Bradley DeMarco, Chao Quan, Richard D. Bunker, Kevin J. Lumb, Bernhard Fasching, John C. Castle, Sharon A. Townson and Débora Bonenfant

Nat Commun, 2025, 16
DOI: 10.1038/s41467-025-65094-3

Exploring the target scope of KEAP1 E3 ligase-based PROTACs

Guangyan Du, Jie Jiang, Nathaniel J. Henning, Nozhat Safaee, Eriko Koide, Radosław P. Nowak, Katherine A. Donovan, Hojong Yoon, Inchul You, Hong Yue, Nicholas A. Eleuteri, Zhixiang He, Zhengnian Li, Hubert T. Huang, Jianwei Che, Behnam Nabet, Tinghu Zhang, Eric S. Fischer and Nathanael S. Gray

Cell Chemical Biology, 2022, 29, 1470
DOI: 10.1016/j.chembiol.2022.08.003

Discovery and Characterization of a First-In-Class HCK/BTK PROTAC DFCI-002-06 for the Treatment of MYD88 Mutated B Cell Malignancies

John M. Hatcher, Shirong Liu, Amanda Kofides, Alexa Canning, Dominic Pizzarella, Xia Liu, Nickolas Tsakmaklis, Maria Guerrera, Christopher Patterson, Alberto Guijosa, Prafulla Gokhale, Zachary Hunter, Shayna Sarosiek, Jorge Castillo, Jinhua Wang, Sara J. Buhrlage and Steven P. Treon

J. Med. Chem., 2026, 69, 1119
DOI: 10.1021/acs.jmedchem.5c02444

Proteolysis‐Targeting Chimera (PROTAC): Current Applications and Future Directions

Gang Fan, Shilin Chen, Qingping Zhang, Na Yu, Ziyang Shen, Zhaoji Liu, Weiming Guo, Zhihan Tang, Jing Yang and Miao Liu

MedComm, 2025, 6
DOI: 10.1002/mco2.70401

Targeting CRBN With Thalidomide Suppresses Fibrosis After Glaucoma Drainage Surgery Through NF-κB Pathway Inhibition

Lijun Wang, Hongsong Li, Lei Xiong, Chao Sun and Jianming Wang

Invest. Ophthalmol. Vis. Sci., 2026, 67, 48
DOI: 10.1167/iovs.67.3.48

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)

Ming He, Chaoguo Cao, Zhihao Ni, Yongbo Liu, Peilu Song, Shuang Hao, Yuna He, Xiuyun Sun and Yu Rao

Sig Transduct Target Ther, 2022, 7
DOI: 10.1038/s41392-022-00999-9

Development of a highly potent and selective degrader of LRRK2

John M. Hatcher, Monika Zwirek, Adil R. Sarhan, Prasanna S. Vatsan, Francesca Tonelli, Dario R. Alessi, Paul Davies and Nathanael S. Gray

Bioorganic & Medicinal Chemistry Letters, 2023, 94, 129449
DOI: 10.1016/j.bmcl.2023.129449

Recent Advances in PROTAC-Based Antiviral Strategies

Haleema Ahmad, Bushra Zia, Hashir Husain and Afzal Husain

Vaccines, 2023, 11, 270
DOI: 10.3390/vaccines11020270

Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues

Marta Pichlak, Tomasz Sobierajski, Katarzyna M. Błażewska and Edyta Gendaszewska-Darmach

Journal of Enzyme Inhibition and Medicinal Chemistry, 2023, 38
DOI: 10.1080/14756366.2023.2254012

Mechanistic Studies and a Retrospective Cohort Study: The Interaction between PPAR Agonists and Immunomodulatory Agents in Multiple Myeloma

Jian Wu, Emily Chu, Barry Paul and Yubin Kang

Cancers, 2022, 14, 5272
DOI: 10.3390/cancers14215272

Targeting Smurf1 to block PDK1–Akt signaling in KRAS-mutated colorectal cancer

Zhiqiang Peng, Wei Fang, Bo Wu, Ming He, Shaohua Li, Jun Wei, Yang Hao, Lujia Jin, Mingqiu Liu, Xin Zhang, Yange Wei, Yingwei Ge, Yinghua Wei, Haili Qian, Yangjun Zhang, Junyi Jiang, Zhijie Chang, Yu Rao, Xueli Zhang, Chun-Ping Cui and Lingqiang Zhang

Nat Chem Biol, 2025, 21, 59
DOI: 10.1038/s41589-024-01683-5

Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins

Yuen Lam Dora Ng, Aleša Bricelj, Jacqueline A. Jansen, Arunima Murgai, Kirsten Peter, Katherine A. Donovan, Michael Gütschow, Jan Krönke, Christian Steinebach and Izidor Sosič

J. Med. Chem., 2023, 66, 4703
DOI: 10.1021/acs.jmedchem.2c01817

Novel strategies and promising opportunities for targeted protein degradation: An innovative therapeutic approach to overcome cancer resistance

Huanjie Zhu, Jin Wang, Qingqing Zhang, Xiaoyan Pan and Jie Zhang

Pharmacology & Therapeutics, 2023, 244, 108371
DOI: 10.1016/j.pharmthera.2023.108371

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity**

Habib Bouguenina, Andrea Scarpino, Jack A. O'Hanlon, Justin Warne, Hannah Z. Wang, Laura Chan Wah Hak, Amine Sadok, P. Craig McAndrew, Mark Stubbs, Olivier A. Pierrat, Tamas Hahner, Marc P. Cabry, Yann‐Vaï Le Bihan, Costas Mitsopoulos, Fernando J. Sialana, Theodoros I. Roumeliotis, Rosemary Burke, Rob L. M. van Montfort, Jyoti Choudhari, Rajesh Chopra, John J. Caldwell and Ian Collins

ChemBioChem, 2023, 24
DOI: 10.1002/cbic.202300351

Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera

Adam G. Bond, Miquel Muñoz i Ordoño, Celia M. Bisbach, Conner Craigon, Nikolai Makukhin, Elizabeth A. Caine, Manjula Nagala, Marjeta Urh, Georg E. Winter, Kristin M. Riching and Alessio Ciulli

J. Am. Chem. Soc., 2024, 146, 33675
DOI: 10.1021/jacs.4c11556

Inhibition of equilibrative nucleoside transporters 1 and 2 by proteolysis-targeting chimeras (PROTACs)

Patricia A. Vignaux, Lucy J. Martinez Guerrero, Renuka Raman, Thomas R. Lane, Javier Perez, Dominique O. Farrera, Stephen H. Wright, Nathan J. Cherrington and Sean Ekins

The Journal of Pharmacology and Experimental Therapeutics, 2025, 392, 103635
DOI: 10.1016/j.jpet.2025.103635

Design and characterization of a heterobifunctional degrader of KEAP1

Hao Chen, Nghi H. Nguyen, Charlene M. Magtoto, Simon A. Cobbold, Grace M. Bidgood, Lizeth G. Meza Guzman, Lachlan W. Richardson, Jason Corbin, Amanda E. Au, Bernhard C. Lechtenberg, Rebecca Feltham, Kate D. Sutherland, Christoph Grohmann, Sandra E. Nicholson and Brad E. Sleebs

Redox Biology, 2023, 59, 102552
DOI: 10.1016/j.redox.2022.102552

Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation

Jianyu Yan, Tengfei Li, Zhenyuan Miao, Pei Wang, Chunquan Sheng and Chunlin Zhuang

J. Med. Chem., 2022, 65, 8798
DOI: 10.1021/acs.jmedchem.2c00728