Efficient, multi-hundred-gram scale access to E3 ubiquitin ligase ligands for degrader development

Mark S. Cooper, Mark C. Norley, Simon Armitage, Joel O. Cresser-Brown, Anthony K. Edmonds, Sean Goggins, Jonathan P. Hopewell, Burhan Karadogan, Kevin A. Knights, Toby J. Nash, Catherine S. Oakes, William J. O'Neill, Simon J. Pridmore, Hannah J. Maple and Graham P. Marsh

Org. Biomol. Chem., 2023, 21, 8344
DOI: 10.1039/D3OB00983A

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

Use of ionic liquids in amidation reactions for proteolysis targeting chimera synthesis

Michela Eleuteri, Jenny Desantis, Gabriele Cruciani, Raimondo Germani and Laura Goracci

Org. Biomol. Chem., 2024, 22, 3477
DOI: 10.1039/D4OB00304G

An effective strategy for balancing energy and sensitivity: design, synthesis, and properties of chimeric energetic molecules

Yujia Shan, Shi Huang, Tianyu Jiang, Ye Cao, Jinxin Wang, Yuteng Cao and Wenquan Zhang

J. Mater. Chem. A, 2025, 13, 1164
DOI: 10.1039/D4TA06644H

PROTAC approaches against drug-resistant EGFRC797S/L858R/T790M mutants: biological evaluation and SAR studies (2020–2025)

Ankush Kumar, Vishakha Sharma, Pallvi Kumari, Rajwinder Kaur and Rohit Bhatia

RSC Med. Chem., 2026
DOI: 10.1039/D5MD01113B

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

Photocatalytic hydro-fluorosulfonylation of alkenes with N-fluorosulfonyl aldimines

Xiang Zhou, Sheng-Cai Wang, Qi-Long Chen, Zi-Yan Zhang, Yan-Shi Xiong, Gui Lu and Jiang Weng

Green Chem., 2025, 27, 2471
DOI: 10.1039/D4GC06205A

Characterizing the Cooperative Effect of PROTAC Systems with End-Point Binding Free Energy Calculation

Kexin Xu, Zhe Wang, Sutong Xiang, Rongfan Tang, Qirui Deng, Jingxuan Ge, Zhiliang Jiang, Kaimo Yang, Tingjun Hou and Huiyong Sun

J. Chem. Inf. Model., 2024, 64, 7666
DOI: 10.1021/acs.jcim.4c01227

Casitas b cell lymphoma‑B (Cbl-b): A new therapeutic avenue for small-molecule immunotherapy

Xiuqi Hu, Erdong Li, Yangguo Zhou, Qidong You and Zhengyu Jiang

Bioorganic & Medicinal Chemistry, 2024, 102, 117677
DOI: 10.1016/j.bmc.2024.117677

Exploring the landscape of post-translational modification in drug discovery

Yuhao Cao, Tianyi Yu, Ziang Zhu, Yuanjiao Zhang, Shanliang Sun, Nianguang Li, Chunyan Gu and Ye Yang

Pharmacology & Therapeutics, 2025, 265, 108749
DOI: 10.1016/j.pharmthera.2024.108749

Chimeric peptide-engineered photodynamic PD-L1 degrader for activating colorectal cancer immunity in combination with exosomal PD-L1 inhibition

Yuxuan Wei, Zuxiao Chen, Wenfeng Zhu, Rongrong Zheng, Chuyu Huang, Ni Yang, Jing Wen, Dawei Zhang, Hong Cheng and Shiying Li

Sci. China Mater., 2025, 68, 2928
DOI: 10.1007/s40843-025-3431-y

Senolytic Prodrugs: A Promising Approach to Enhancing Senescence‐Targeting Intervention

Mengyang Chang, Yue Dong, Alexis B. Cruickshank‐Taylor, Giri Gnawali, Fangchao Bi and Wei Wang

ChemBioChem, 2024, 25
DOI: 10.1002/cbic.202400355

Design and synthetic approaches to thalidomide based small molecule degraders

Ajeet Kumar, Gulshan Kumar, Nidhi Kalia and Priya Ranjan Sahoo

European Journal of Medicinal Chemistry, 2025, 293, 117700
DOI: 10.1016/j.ejmech.2025.117700

Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection

Lei Tian, Taotao Qiang, Xiuding Yang, Yue Gao, Xiaopei Zhai, Kairui Kang, Cong Du, Qi Lu, Hong Gao, Dezhu Zhang, Xiaolin Xie and Chengyuan Liang

European Journal of Medicinal Chemistry, 2024, 264, 115979
DOI: 10.1016/j.ejmech.2023.115979

Unveiling New Triazoloquinoxaline‐Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9

Martina Pierri, Guglielmo Bove, Erica Gazzillo, Ester Colarusso, Francesca Scala, Giacomo Pepe, Stefania Terracciano, Maria Giovanna Chini, Nicla Simonelli, Ines Bruno, Angela Nebbioso, Pietro Campiglia, Giuseppe Bifulco, Lucia Altucci, Nunzio Del Gaudio and Gianluigi Lauro

Chemistry A European J, 2025, 31
DOI: 10.1002/chem.202404218

Stimuli‐Responsive PROTACs for Controlled Protein Degradation

Keli An, Xuqian Deng, Hongli Chi, Yuchao Zhang, Yan Li, Ming Cheng, Zhigang Ni, Zhi Yang, Chao Wang, Jinling Chen, Jianbo Bai, Chunyan Ran, Yong Wei, Juan Li, Penghui Zhang, Feng Xu and Weihong Tan

Angew Chem Int Ed, 2023, 62
DOI: 10.1002/anie.202306824

Discovery of PXR Antagonist MI891 and PXR Degrader MI1013 and Their Roles in Hepatic Gene Regulation

Rajamanikkam Kamaraj, Ivana Mejdrová, Maria Krutakova, Tomas Smutny, Kryštof Škach, Klara Dohnalova, Lucie Smutna, Dharani Sai Sreekanth Nellore, Jan Dusek, Karel Chalupsky, Jana Hricová, Thales Kronenberger, Aaron Stahl, Markus Templin, Albert Braeuning, Radim Nencka and Petr Pavek

J. Med. Chem., 2025, 68, 14271
DOI: 10.1021/acs.jmedchem.4c03134

Pt(IV)-PROTAC Complexes with Synergistic Antitumor Activity and Enhanced Membrane Permeability

Cheng-xin Li, Zhi-ru Zou, Shan Xu, Jia-hui Shi, Yong Zou, Ming Yan and Xue-jing Zhang

J. Med. Chem., 2025, 68, 8208
DOI: 10.1021/acs.jmedchem.4c02909

Non-invasive in vivo monitoring of PROTAC-mediated protein degradation using an environment-sensitive reporter

Tao Li, Qingyu Zong, He Dong, Ihsan Ullah, Zhenhai Pan and Youyong Yuan

Nat Commun, 2025, 16
DOI: 10.1038/s41467-025-57191-0

Recent advances in the molecular design and applications of proteolysis targeting chimera-based multi-specific antiviral modality

Yang Zhou, Shujing Xu, Nerea López-Carrobles, Dang Ding, Xinyong Liu, Luis Menéndez-Arias and Peng Zhan

Acta Materia Medica, 2023, 2
DOI: 10.15212/AMM-2023-0019

PROTACs in the Management of Prostate Cancer

Poornachandra Yedla, Ahmed O. Babalghith, Vindhya Vasini Andra and Riyaz Syed

Molecules, 2023, 28, 3698
DOI: 10.3390/molecules28093698

Nano Proteolysis Targeting Chimeras (PROTACs) with Anti‐Hook Effect for Tumor Therapy

Ni‐Yuan Zhang, Da‐Yong Hou, Xing‐Jie Hu, Jian‐Xiao Liang, Man‐Di Wang, Zhang‐Zhi Song, Li Yi, Zhi‐Jia Wang, Hong‐Wei An, Wanhai Xu and Hao Wang

Angew Chem Int Ed, 2023, 62
DOI: 10.1002/anie.202308049

FAK inhibitors in cancer, a patent review – an update on progress

Ya-Xi Ye, Yu-Yao Cao, Li-Sheng Xu, Hai-Chao Wang, Xin-Hua Liu and Hai-Liang Zhu

Expert Opinion on Therapeutic Patents, 2024, 34, 593
DOI: 10.1080/13543776.2024.2368742

Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy

Changyong Guo, Fei Gao, Guoyuan Wu, Jinqiu Li, Chunquan Sheng, Shipeng He and Honggang Hu

Advanced Science, 2025, 12
DOI: 10.1002/advs.202410778

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

Discovery of the cereblon-recruiting tubulin PROTACs effective in overcoming Taxol resistance in vitro and in vivo

Hua Yang, Jinling Qin, Yuanyuan Pei, Sumeng Guan, Mei Zhao, Yingge Wang, Yongfang Yao, Yongtao Duan and Moran Sun

European Journal of Medicinal Chemistry, 2024, 265, 116067
DOI: 10.1016/j.ejmech.2023.116067

HerTACs Enable Tumor‐Selective Lysosomal Degradation of Membrane and Extracellular Proteins via HER2 Trafficking

Shipeng He, Wenjing Huang, Yaojin Zhu, Fei Gao, Yuxin Fang, Jiayi Zhu, Yuhan Bao, Guoqiang Dong and Chunquan Sheng

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202511467

Targeting the undruggables—the power of protein degraders

Chao Zhang, Yongbo Liu, Guangchen Li, Zhouli Yang, Chi Han, Xiuyun Sun, Chunquan Sheng, Ke Ding and Yu Rao

Science Bulletin, 2024, 69, 1776
DOI: 10.1016/j.scib.2024.03.056

Advances in KEAP1-based PROTACs as emerging therapeutic modalities: Structural basis and progress

Jing Chen, Disheng Feng, Rui Zhu, Hua Li and Lixia Chen

Redox Biology, 2025, 85, 103781
DOI: 10.1016/j.redox.2025.103781

Opportunities and challenges of PROTAC in the treatment of protein-driven diseases

Zhe Zhou, Peng Liu, Yang Li, Xuelian Liu and Jinyao Li

Results in Chemistry, 2026, 24, 103234
DOI: 10.1016/j.rechem.2026.103234

Advances in light-controllable PROTACs: Design strategies, therapeutic applications and current challenges

Ji Wu, Zi-Yue Wang, Shi-Xuan Tan, Ting-Yu Li, Bing-Bing Chen, Qi-Qi Chen, Hao Li, Jin-Bo Niu, Xiang-Jing Fu, Jian Song and Sai-Yang Zhang

Bioorganic Chemistry, 2026, 169, 109380
DOI: 10.1016/j.bioorg.2025.109380

Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC

Jiexuan Chen, Mingfei Wu, Jun Mo, Ju Hong, Wei Wang, Yuheng Jin, Xinfei Mao, Xueyan Liao, Kailin Li, Xiaoli Yu, Sikang Chen, Shenxin Zeng, Wenhai Huang, Hongxia Xu, Jian Wu, Ji Cao, Yubo Zhou, Meidan Ying, Chengliang Zhu, Qiaojun He, Bo Zhang, Nengming Lin, Xiaowu Dong and Jinxin Che

J. Med. Chem., 2025, 68, 8010
DOI: 10.1021/acs.jmedchem.4c02438

Advancements in PROTAC-based therapies for neurodegenerative diseases

Deyuan Kong, Liying Meng, Pengfei Lin and Guanzhao Wu

Future Medicinal Chemistry, 2025, 17, 591
DOI: 10.1080/17568919.2025.2463310

Targeted degradation of CDK4/6 by LA-CB1 inhibits EMT and suppresses tumor growth in orthotopic breast cancer

Jingliang He, Shunfang Liu, Siyi Zhang, Qi Gao, Lan Zhu, Ningyang Xu, Zhongke Hu, Xingyu Zhang, Shaojie Ma, Xiujun Wang, Bin Liu and Wei Liu

Sci Rep, 2025, 15
DOI: 10.1038/s41598-025-92494-8

Targeted protein degradation in cancers: Orthodox PROTACs and beyond

Jin Li, Xinxin Chen, Aiping Lu and Chao Liang

The Innovation, 2023, 4, 100413
DOI: 10.1016/j.xinn.2023.100413

PROTACs as novel therapeutics against Mycobacterium tuberculosis: Current progress and future directions

Deepthi Ramesh and Ahammed Ameen Thottasseri

European Journal of Medicinal Chemistry, 2026, 308, 118718
DOI: 10.1016/j.ejmech.2026.118718

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

Analyzing the Linker Structure of PROTACs throughout the Induction Process: Computational Insights

Yihao Li, Xiaoxuan Zhang, Jiali Xie, Dan Meng, Ming Liu, Yuxiang Chang, Guangrong Feng, Junhao Jiang and Ping Deng

J. Med. Chem., 2025, 68, 3420
DOI: 10.1021/acs.jmedchem.4c02637

Exploiting ELIOT for Scaffold-Repurposing Opportunities: TRIM33 a Possible Novel E3 Ligase to Expand the Toolbox for PROTAC Design

Tommaso Palomba, Giusy Tassone, Carmine Vacca, Matteo Bartalucci, Aurora Valeri, Cecilia Pozzi, Simon Cross, Lydia Siragusa and Jenny Desantis

IJMS, 2022, 23, 14218
DOI: 10.3390/ijms232214218

Discovery of small molecule degraders for modulating cell cycle

Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai and Yu Rao

Front. Med., 2023, 17, 823
DOI: 10.1007/s11684-023-1027-5

Design and evaluation of anaplastic lymphoma kinase degraders using a covalent fumarate handle

Namsik Yu, Ji-Eun Lee, Seulki Park, Su Kyeong Yun, Do Hyun Ryu, Jung-Ae Kim, Jeong-Hoon Kim and Jong Yeon Hwang

Bioorganic & Medicinal Chemistry Letters, 2025, 117, 130075
DOI: 10.1016/j.bmcl.2024.130075

Synergistic DNA repair inhibition and genotoxic therapy in cisplatin-resistant tumors via microneedle-based co-delivery of PROTAC and Pt(IV)

Shenghui Wang, Runze Zhao, Mingge Hou, Xiyun Yan and Bing Jiang

Nano Research, 2025, 18, 94907963
DOI: 10.26599/NR.2025.94907963

The Functions and Regulatory Chemicals of Human Leucine Zipper Transcription Factors (LZ TFs)

Hanming Yang, Shuyang Bi, Biao Yu, Pengfei Fang and Jing Wang

Acta Chimica Sinica, 2025, 83, 725
DOI: 10.6023/A25020042

Alkenyl oxindole is a novel PROTAC moiety that recruits the CRL4DCAF11 E3 ubiquitin ligase complex for targeted protein degradation

Ying Wang, Tianzi Wei, Man Zhao, Aima Huang, Fan Sun, Lu Chen, Risheng Lin, Yubao Xie, Ming Zhang, Shiyu Xu, Zhihui Sun, Liang Hong, Rui Wang, Ruilin Tian, Guofeng Li and Alessio Ciulli

PLoS Biol, 2024, 22, e3002550
DOI: 10.1371/journal.pbio.3002550

An ultrasound-activated PROTAC prodrug with self-reporting fluorescence for targeted protein degradation

Tao Li, Yalan Tu, He Dong, Wenjiao Xie, Xiaoyu Pan and Youyong Yuan

Biomaterials, 2026, 330, 124045
DOI: 10.1016/j.biomaterials.2026.124045

Rapid PROTAC Discovery Platform: Nanomole-Scale Array Synthesis and Direct Screening of Reaction Mixtures

Mateusz P. Plesniak, Emilia K. Taylor, Frederik Eisele, Christopher M. B. K. Kourra, Iacovos N. Michaelides, Alice Oram, Johan Wernevik, Zulma Santisteban Valencia, Hannah Rowbottom, Nadia Mann, Linda Fredlund, Valentyna Pivnytska, Anna Novén, Mohammad Pirmoradian, Thomas Lundbäck, R. Ian Storer, Mariell Pettersson, Gian M. De Donatis and Marie Rehnström

ACS Med. Chem. Lett., 2023, 14, 1882
DOI: 10.1021/acsmedchemlett.3c00314

Rapid and high-throughput screening of proteolysis targeting chimeras using a dual-reporter system expressing fluorescence protein and luciferase

Shuai Meng, Yuan Meng, Xuena Yang, Wenwen Yu, Bole Li, Tianjun Liu, Jie Zhang, Xiubao Ren and Lin Zhang

BMC Biol, 2025, 23
DOI: 10.1186/s12915-025-02153-7

NDA Submission of Vepdegestrant (ARV-471) to U.S. FDA: The Beginning of a New Era of PROTAC Degraders

Zonghui Ma and Jia Zhou

J. Med. Chem., 2025, 68, 14129
DOI: 10.1021/acs.jmedchem.5c01818

The pan-cancer proteome atlas, a mass spectrometry-based landscape for discovering tumor biology, biomarkers, and therapeutic targets

Jaco C. Knol, Mengge Lyu, Franziska Böttger, Madalena Nunes Monteiro, Thang V. Pham, Frank Rolfs, Andrea Vallés-Martí, Tim Schelfhorst, Richard R. de Goeij-de Haas, Irene V. Bijnsdorp, Shuaiyao Wang, Fangfei Zhang, Jun A, Bart A. Westerman, Barbara Sitek, Janne Lehtiö, Jan Koster, Jan N.M. IJzermans, Hanneke W.M. van Laarhoven, Maarten F. Bijlsma, Jan Paul Medema, Alex A. Henneman, Sander R. Piersma, Ruud H. Brakenhoff, Jacqueline Cloos, Valentina Cordo', Daphne de Jong, Geert Kazemier, Danijela Koppers-Lalic, Mariette Labots, Tessa Y.S. Le Large, John W.M. Martens, Jules P.P. Meijerink, Madiha Mumtaz, Chantal Scheepbouwer, Robby E. Kibbelaar, David P. Noske, Renske D.M. Steenbergen, Nicole C.T. van Grieken, Winan van Houdt, Elisa Giovannetti, Geert J.L.H. van Leenders, Jos Jonkers, Tong Liu, Meisi Yan, Xiaolu Zhan, Tiannan Guo and Connie R. Jimenez

Cancer Cell, 2025, 43, 1328
DOI: 10.1016/j.ccell.2025.05.003

Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research

Xiang Li, Qian Liu, Xin Xie, Cheng Peng, Qiwen Pang, Bo Liu and Bo Han

J. Med. Chem., 2023, 66, 1700
DOI: 10.1021/acs.jmedchem.2c01712

Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

Shuang Xiang and Xiaoyun Lu

Acta Pharmaceutica Sinica B, 2024, 14, 517
DOI: 10.1016/j.apsb.2023.11.010

Next‐Generation Proteolysis‐Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation

Mohamed S. Nafie, Mohamed K. Diab, Asmaa S. A. Yassen, Amany M. Elshamy, Mohamed R. El Tohamy, Haytham O. Tawfik and Sherif Ashraf Fahmy

Drug Development Research, 2025, 86
DOI: 10.1002/ddr.70192

Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy

Zhi-feng Zou, Lei Yang, Hui-jun Nie, Jing Gao, Shu-min Lei, Yi Lai, Fan Zhang, Ernst Wagner, Hai-jun Yu, Xiao-hua Chen and Zhi-ai Xu

Acta Pharmacol Sin, 2024, 45, 1740
DOI: 10.1038/s41401-024-01266-z

Small-molecule-based targeted therapy in liver cancer

Yue Ming, Yanqiu Gong, Xuewen Fu, Xinyu Ouyang, Yong Peng and Wenchen Pu

Molecular Therapy, 2024, 32, 3260
DOI: 10.1016/j.ymthe.2024.08.001

Dynamic characteristics of proteolysis-targeting chimera systems revealed by in silico computations

Kexin Xu, Jingxuan Ge, Rongfan Tang, Tingjun Hou and Huiyong Sun

Current Opinion in Structural Biology, 2025, 95, 103151
DOI: 10.1016/j.sbi.2025.103151

Ligation to Scavenging Strategy Enables On-Demand Termination of Targeted Protein Degradation

Yuhui Jin, Jing Fan, Ruyan Wang, Xuanyu Wang, Ning Li, Qidong You and Zhengyu Jiang

J. Am. Chem. Soc., 2023, 145, 7218
DOI: 10.1021/jacs.2c12809

Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)

Jianchao Zhang, Xiao Chen, Congli Chen, Fengming Li, Xiaoxiao Song, Chaowei Liu, Kefan Liao, Ming-Yuan Su, Chris Soon Heng Tan, Lijing Fang and Hai Rao

J. Med. Chem., 2024, 67, 13666
DOI: 10.1021/acs.jmedchem.4c00208

A one-pot photocatalytic triazole-based linkerology for PROTACs

Jinhua Liu, Yaqi Deng, Jiabin Yin, Jian Ji, Cong Guan, Xuwen Chen, Xiang Wu, Tong Zhu and Shunying Liu

Cell Reports Physical Science, 2024, 5, 102139
DOI: 10.1016/j.xcrp.2024.102139

Molecular Glue Degraders Redefining Targeted Therapies From Discovery to Therapeutic Applications

Jinfeng Wen, Jingtian Yu, Wuqiang Wen and Baishan Jiang

MedComm – Oncology, 2026, 5
DOI: 10.1002/mog2.70058

Senolysis Enabled by Senescent Cell‐Sensitive Bioorthogonal Tetrazine Ligation

Mengyang Chang, Yue Dong, Hang Xu, Alexis B. Cruickshank‐Taylor, Jacob S. Kozora, Baran Behpour and Wei Wang

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202315425

Tailoring albumin-based theranostic PROTACs nanoparticles for enhanced NIR-II bioimaging and synergistic cancer chemo-phototherapy

Zhuang Hu, Ruihan Li, Xinyue Cui, Changjun Hu and Zilin Chen

Chemical Engineering Journal, 2023, 469, 143883
DOI: 10.1016/j.cej.2023.143883

Design, synthesis, and pharmacological evaluation of novel PROTAC degraders targeting 11β-HSD1 for metabolic disease intervention

Liguo Wang, Xue Tao, Ming He, Yu Lu, Yuji Wang and Juanjuan Zhu

Bioorganic Chemistry, 2026, 174, 109731
DOI: 10.1016/j.bioorg.2026.109731

Self-assembled Nano-PROTACs: bridging chemical design and biological barriers in targeted protein degradation

Ni-Yuan Zhang, Jian-Xiao Liang, Bei-Ning Hu, Yi Wang, Hong-Wei An and Hao Wang

Advanced Drug Delivery Reviews, 2026, 115861
DOI: 10.1016/j.addr.2026.115861

Split‐Deliver‐Click: Tumor‐Specific Protein Degradation via “AND” Logic‐Gated In‐Cell Bioorthogonal Clicking of PROTACs

He Dong, Cilong Chu, Ihsan Ullah, Qing Xu, Zhenhai Pan and Youyong Yuan

Angewandte Chemie, 2026, 138
DOI: 10.1002/ange.202520774

Discovery of Novel PROTAC Degraders of p300/CBP as Potential Therapeutics for Hepatocellular Carcinoma

Qi Chang, Jiayi Li, Yue Deng, Ruilin Zhou, Bingwei Wang, Yujie Wang, Mingming Zhang, Xun Huang and Yingxia Li

J. Med. Chem., 2024, 67, 2466
DOI: 10.1021/acs.jmedchem.3c01468

In Situ PROTAC Synthesis Enabled by Pathologically Activated Bioorthogonal Catalysis for Precision Cancer Therapy

Dilan Ouyang, Rongjin Yang, Yuhang Yao, Fang Jiang, Sijie Song, Yuheng Yang, Edikan A. Ogunnaike, Zhitong Chen, Zhaowei Chen and Huanghao Yang

J. Am. Chem. Soc., 2025, 147, 39987
DOI: 10.1021/jacs.5c15945

Research progress of dual-targeting CDKs regulators for cancer therapy

Fei-Xia Yue, Ya-Lan Wang, Rui-Yan, Guo-Qing Chen, Xiaoting Li and Qing-Kun Shen

Bioorganic Chemistry, 2025, 163, 108769
DOI: 10.1016/j.bioorg.2025.108769

From PROTAC to TPD: Advances and Opportunities in Targeted Protein Degradation

Siqi Wang, Fuchu He, Chunyan Tian and Aihua Sun

Pharmaceuticals, 2024, 17, 100
DOI: 10.3390/ph17010100

De Novo Design of Hexamer‐Linker Dual‐Action Nano‐PROTAC for Tumor‐Specific Ferroptosis

Ni‐Yuan Zhang, Zhuan Wen, Ming‐Ze Cai, Ke‐Ting Zhou, Hao‐Ze Li, Yi‐xuan Liu, Shang Wu, Yu Xia, Hong‐Wei An and Hao Wang

Angew Chem Int Ed, 2026, 65
DOI: 10.1002/anie.202509924

Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

Qiong Li, Li Zhou, Siyuan Qin, Zhao Huang, Bowen Li, Ruolan Liu, Mei Yang, Edouard C. Nice, Huili Zhu and Canhua Huang

European Journal of Medicinal Chemistry, 2023, 257, 115447
DOI: 10.1016/j.ejmech.2023.115447

PROTACs: Novel tools for improving immunotherapy in cancer

Shizhe Li, Ting Chen, Jinxin Liu, He Zhang, Jiatong Li, Zhiwei Wang and Guanning Shang

Cancer Letters, 2023, 560, 216128
DOI: 10.1016/j.canlet.2023.216128

Solid‐Phase Parallel Synthesis of Photocleavable Bifunctional Molecules Enables Efficient Phenotypic Protein Degrader Discovery

Baoli Ding, Jiawen Hu, Rongtian Zhang, Binyan Shou, Mengdie Chen, Li Jiang, Meng Yuan, Bo Yang, Qiaojun He, Ji Cao and Cheng‐Liang Zhu

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202424118

Deubiquitinase-Targeting Chimeras (DUBTACs) as a Potential Paradigm-Shifting Drug Discovery Approach

Zonghui Ma, Mingxiang Zhou, Haiying Chen, Qiang Shen and Jia Zhou

J. Med. Chem., 2025, 68, 6897
DOI: 10.1021/acs.jmedchem.4c02975

Design of RGD-functionalized GSH-responsive pegylated polymeric protacs for selective BRD4 degradation and EndMT-driven cardiac fibrosis inhibition

Tao Bi, Lei Chen, Ting Wang, Wenjun Miao, Silong Zhai, Rui Huang, Qin Sun, Yihan Chen, Hongna Su, Jie Zhou, Ruowen Li, Weixue Huang, Xiaojun Yao, Pei Luo and Zengjin Liu

J Nanobiotechnol, 2026, 24
DOI: 10.1186/s12951-026-04036-7

Efficient green synthesis of the targeted proteolysis system component

Maria A. Zakharova, Mikhail Vasil'evich Chudinov, Maxim E. Zhuravlev and Alexei Yur'evich Lukin

Mendeleev Communications, 2026, 36, 295
DOI: 10.71267/mencom.7928

Discovery of the first potent ROR1 degrader for the treatment of non-small cell lung cancer

Jinlin Li, Lin Li, Caiyun Hou, Zhaodi Tian, Yang Zhou, Jinwei Zhang, Xiaomei Ren, Zhen Wang, Weixue Huang, Ke Ding and Fengtao Zhou

European Journal of Medicinal Chemistry, 2025, 286, 117325
DOI: 10.1016/j.ejmech.2025.117325

In Vivo Self‐Assembly of PROTACs by Bioorthogonal Chemistry for Precision Cancer Therapy

Shaowen Xie, Jingjie Zhu, Yihan Peng, Fangyi Zhan, Feiyan Zhan, Chen He, Dazhi Feng, Jia Xie, Jingyu Liu, Huajian Zhu, Hong Yao, Jinyi Xu, Zhigui Su and Shengtao Xu

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202421713

Recent advances of PROTACs technology in neurodegenerative diseases

Chao Wang, Yujing Zhang, Shanbo Yang and Dongming Xing

Arabian Journal of Chemistry, 2023, 16, 105015
DOI: 10.1016/j.arabjc.2023.105015

PROTACs targeting epigenetic proteins

Chao Zhang, Yuna He, Xiuyun Sun, Wenyi Wei, Yanlong Liu and Yu Rao

Acta Materia Medica, 2023, 2
DOI: 10.15212/AMM-2023-0039

Targeted delivery of PROTAC-based prodrug activated by bond-cleavage bioorthogonal chemistry for microneedle-assisted cancer therapy

Jing Huang, Zhuo Yao, Bowen Li and Yuan Ping

Journal of Controlled Release, 2023, 361, 270
DOI: 10.1016/j.jconrel.2023.07.062

Versatile Split-and-Mix Liposome PROTAC Platform for Efficient Degradation of Target Protein In Vivo

Chunli Song, Zijun Jiao, Zhanfeng Hou, Yun Xing, Xinrui Sha, Yuechen Wang, Jiaxin Chen, Susheng Liu, Zigang Li and Feng Yin

JACS Au, 2024, 4, 2915
DOI: 10.1021/jacsau.4c00278

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

HerTACs Enable Tumor‐Selective Lysosomal Degradation of Membrane and Extracellular Proteins via HER2 Trafficking

Shipeng He, Wenjing Huang, Yaojin Zhu, Fei Gao, Yuxin Fang, Jiayi Zhu, Yuhan Bao, Guoqiang Dong and Chunquan Sheng

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202511467

De Novo Design of Hexamer‐Linker Dual‐Action Nano‐PROTAC for Tumor‐Specific Ferroptosis

Ni‐Yuan Zhang, Zhuan Wen, Ming‐Ze Cai, Ke‐Ting Zhou, Hao‐Ze Li, Yi‐xuan Liu, Shang Wu, Yu Xia, Hong‐Wei An and Hao Wang

Angewandte Chemie, 2026, 138
DOI: 10.1002/ange.202509924

Small-Molecule PROTACs for Cancer Immunotherapy

Zefan Liu, Yajun Zhang, Yucheng Xiang and Xin Kang

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

An updated patent review of BRD4 degraders

Zonghui Ma, Cun Zhang, Andrew A. Bolinger and Jia Zhou

Expert Opinion on Therapeutic Patents, 2024, 34, 929
DOI: 10.1080/13543776.2024.2400166

Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2)

Zonghui Ma, Andrew A. Bolinger, Haiying Chen and Jia Zhou

J. Med. Chem., 2023, 66, 10991
DOI: 10.1021/acs.jmedchem.3c00948

Discovery of a Potent, selective and orally bioavailable CDK9 degrader for targeting transcription regulation in Triple-Negative breast cancer

Hui-Jun Nie, Ben-Fu Li, Jingya Sun, Yali Yuan, Zhi-Gao Zhang, Hao Hu, Wen-Jing Wang, Ziqiang Chen, Simei Wang, Wensi Huang, Xingxing Diao, Jinghua Yu, Ruimin Huang and Xiao-Hua Chen

Bioorganic Chemistry, 2024, 153, 107876
DOI: 10.1016/j.bioorg.2024.107876

Integrating Proteolysis‐Targeting Chimeras (PROTACs) with Delivery Systems for More Efficient and Precise Targeted Protein Degradation

Jiachan Lin, Zirui Chen, Dan Zhang, Nan Zhang, Hongzhong Chen and Dong‐Sheng Guo

Macromol. Rapid Commun., 2025, 46
DOI: 10.1002/marc.202401051

A Versatile and Sustainable Multicomponent Platform for the Synthesis of Protein Degraders: Proof-of-Concept Application to BRD4-Degrading PROTACs

Irene Preet Bhela, Alice Ranza, Federica Carolina Balestrero, Marta Serafini, Silvio Aprile, Rita Maria Concetta Di Martino, Fabrizio Condorelli and Tracey Pirali

J. Med. Chem., 2022, 65, 15282
DOI: 10.1021/acs.jmedchem.2c01218

Modular Assembled Targeting Chimera Enables Multimodal Targeted Protein Degradation

Wentao Zhu, Wenqian Zhang, Yinmiao Wang, Jian Chen, Fang Xu and Jiyan Pang

JACS Au, 2025, 5, 5635
DOI: 10.1021/jacsau.5c01131

Proteolysis Targeting Chimeras (PROTACs) based on celastrol induce multiple protein degradation for triple-negative breast cancer treatment

Xuelan Gan, Fan Wang, Jianguo Luo, Yunfei Zhao, Yan Wang, Chao Yu and Jun Chen

European Journal of Pharmaceutical Sciences, 2024, 192, 106624
DOI: 10.1016/j.ejps.2023.106624

Stimuli‐Responsive PROTACs for Controlled Protein Degradation

Keli An, Xuqian Deng, Hongli Chi, Yuchao Zhang, Yan Li, Ming Cheng, Zhigang Ni, Zhi Yang, Chao Wang, Jinling Chen, Jianbo Bai, Chunyan Ran, Yong Wei, Juan Li, Penghui Zhang, Feng Xu and Weihong Tan

Angewandte Chemie, 2023, 135
DOI: 10.1002/ange.202306824

KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma

Dongsheng Ni, Zhaolai Qi, Yuefeng Wang, Yong Man, Jing Pang, Weiqing Tang, Jingzhou Chen, Jian Li and Guoping Li

Experimental Cell Research, 2024, 440, 114117
DOI: 10.1016/j.yexcr.2024.114117

In situ construction of intracellular supramolecular assemblies as an alternative strategy for protein degradation

Xiaoqian Hu, Qingxin Yao, Xiaobo Wu, Jiali Chen, Ruijia Zhang, Yan Zhao and Yuan Gao

Nat Commun, 2025, 16
DOI: 10.1038/s41467-025-61175-5

Development and Mechanistic Evaluation of Cathepsin B‐Activatable Peptide‐Drug Conjugate PROTACs for Targeted Protein Degradation in Malignant Tumors: Advancing Precision Protein Degradation Therapeutics in Oncology

Qingqing Zhang, Yu Liu, Jie Zhang, Hengtao Dong, Xiaoyan Pan and Jie Zhang

Small, 2026, 22
DOI: 10.1002/smll.202506562

An overview of PROTACs: a promising drug discovery paradigm

Zi Liu, Mingxing Hu, Yu Yang, Chenghao Du, Haoxuan Zhou, Chengyali Liu, Yuanwei Chen, Lei Fan, Hongqun Ma, Youling Gong and Yongmei Xie

Mol Biomed, 2022, 3
DOI: 10.1186/s43556-022-00112-0

Discovery of an activatable near-infrared fluorescent and theranostic PROTAC for tumor-targeted detecting and degrading of BRD4

Keliang Li, Guoqiang Dong, Shanchao Wu and Chunquan Sheng

Chinese Chemical Letters, 2025, 36, 110280
DOI: 10.1016/j.cclet.2024.110280

Next-generation cancer therapeutics: PROTACs and the role of heterocyclic warheads in targeting resistance

Ebna Azizal Omar, Rajesh R., Pronoy Kanti Das, Rohit Pal, Gurubasavaraja Swamy Purawarga Matada and Lalmohan Maji

European Journal of Medicinal Chemistry, 2025, 281, 117034
DOI: 10.1016/j.ejmech.2024.117034

Bioorthogonal Sonodynamic Plug‐and‐Play Targeting Chimeras (SDPTAC) for Precise Targeted Protein Degradation

Yuhan Bao, Yaojin Zhu, Xinhao Wei, Yuxin Fang, Jiayi Zhu, Fei Gao, Guoqiang Dong, Shipeng He and Chunquan Sheng

Advanced Science, 2026, 13
DOI: 10.1002/advs.202520975

The roles of E3 ubiquitin ligases in cancer progression and targeted therapy

Chibuzo Sampson, Qiuping Wang, Wuxiyar Otkur, Haifeng Zhao, Yun Lu, Xiaolong Liu and Hai‐long Piao

Clinical & Translational Med, 2023, 13
DOI: 10.1002/ctm2.1204

Discovery of the first selective and potent PROTAC degrader for the pseudokinase TRIB2

Chaowei Wen, Prathibha R. Gajjala, Yihan Liu, Bingzhong Chen, Mehtab S. Bal, Payal Sutaria, Qiao Yuanyuan, Yang Zheng, Yang Zhou, Jinwei Zhang, Weixue Huang, Xiaomei Ren, Zhen Wang, Ke Ding, Arul M. Chinnaiyan and Fengtao Zhou

European Journal of Medicinal Chemistry, 2025, 281, 117016
DOI: 10.1016/j.ejmech.2024.117016

Molecular glue-mediated targeted protein degradation: A novel strategy in small-molecule drug development

Xueqiang Tan, Zuyi Huang, Hairun Pei, Zongchao Jia and Jimin Zheng

iScience, 2024, 27, 110712
DOI: 10.1016/j.isci.2024.110712

High affinity and low PARP-trapping benzimidazole derivatives as a potential warhead for PARP1 degraders

Xiaoyu Peng, Yang Li, Junfeng Qu, Lizhi Jiang, Kaiyue Wu, Dan Liu, Yuping Chen, Junmei Peng, Yu Guo and Xuan Cao

European Journal of Medicinal Chemistry, 2024, 271, 116405
DOI: 10.1016/j.ejmech.2024.116405

Discovery of a Selective and Orally Bioavailable FGFR2 Degrader for Treating Gastric Cancer

Lin Ma, Yingying Li, Ruixiang Luo, Yuhan Wang, Jiaqi Cao, Weitao Fu, Bolan Qian, Lei Zheng, Longguang Tang, Xinting Lv, Lulu Zheng, Guang Liang and Lingfeng Chen

J. Med. Chem., 2023, 66, 7438
DOI: 10.1021/acs.jmedchem.3c00150

Breaking Bad Proteins—Discovery Approaches and the Road to Clinic for Degraders

Corentin Bouvier, Rachel Lawrence, Francesca Cavallo, Wendy Xolalpa, Allan Jordan, Roland Hjerpe and Manuel S. Rodriguez

Cells, 2024, 13, 578
DOI: 10.3390/cells13070578

Discovery of the first ataxia telangiectasia and Rad3-related (ATR) degraders for cancer treatment

Lei Huang, Jialu Shao, Wenwen Lai, Hongfeng Gu, Jieping Yang, Shi Shi, Shepherd Wufoyrwoth, Zhe Song, Yi Zou, Yungen Xu and Qihua Zhu

European Journal of Medicinal Chemistry, 2024, 267, 116159
DOI: 10.1016/j.ejmech.2024.116159

TRL-PROTAC: A pre-trained generator of PROTACs targeting specific proteins optimized by reinforcement learning

Yuhao Dai and Fei Zhu

ComSIS, 2024, 21, 1293
DOI: 10.2298/CSIS240327039D

Linker-free PROTACs efficiently induce the degradation of oncoproteins

Jianchao Zhang, Congli Chen, Xiao Chen, Kefan Liao, Fengming Li, Xiaoxiao Song, Chaowei Liu, Ming-Yuan Su, Huiyong Sun, Tingjun Hou, Chris Soon Heng Tan, Lijing Fang and Hai Rao

Nat Commun, 2025, 16
DOI: 10.1038/s41467-025-60107-7

Ligand-Directed Self-Assembling Chimeras for Targeted Protein O-GlcNAcylation

Zhihao Guo, Tongyang Xu, Khadija Shahed Khan, Stephan Scheeff, Yao Qin, Sin-Yi Yu, Richard Lo, Yuanpei Li, Yalun Xie, Bowen Ma, Yunpeng Huang, Hillary Yui-Yan Yip, Clive Yik-Sham Chung, Tomonori Tamura, Itaru Hamachi and Billy Wai-Lung Ng

ACS Chem. Biol., 2025, 20, 2907
DOI: 10.1021/acschembio.5c00684

BRD4-targeted photodegradation nanoplatform for light activatable melanoma therapy

Shiman Lu, Zhaoqing Shi, Chendi Ding, Wenyan Wang, Weilang Zhang, Li Huang, Jiachan Lin, Xinpei Wang, Ran Luo, Xiaowei Zeng, Wenhu Zhou, Hongzhong Chen, Qiangsong Wang and Lin Mei

Biomaterials, 2025, 317, 123101
DOI: 10.1016/j.biomaterials.2025.123101

MDM2-Based Proteolysis-Targeting Chimeras (PROTACs): An Innovative Drug Strategy for Cancer Treatment

André T. S. Vicente and Jorge A. R. Salvador

IJMS, 2022, 23, 11068
DOI: 10.3390/ijms231911068

Switchable carbo-fluorosulfonylation and hydro-fluorosulfonylation of alkenes enabled by bifunctional fluorosulfonyl radical precursors

Ting Xiong, Qi-Long Chen, Zhi-Da Chen, Ji-Tao Yi, Sheng-Cai Wang, Gui Lu, Albert S.C. Chan and Jiang Weng

Chem Catalysis, 2023, 3, 100821
DOI: 10.1016/j.checat.2023.100821

MALT1 Inhibitors and Degraders: Strategies for NF-κB-Driven Malignancies

Ru-Yue Zhang, Zi-Xuan Wang, Meng-Yuan Zhang, Yu-Fan Wang, Si-Li Zhou, Jia-Lu Xu, Wen-Xuan Lin, Tian-Rui Ji, Ya-Dong Chen, Tao Lu, Nian-Guang Li and Zhi-Hao Shi

J. Med. Chem., 2025, 68, 5075
DOI: 10.1021/acs.jmedchem.4c02873

Targeted protein degradation technologies: Emerging mechanisms and nano-based innovations

Mingge Hou, Runze Zhao, Shenghui Wang, Bing Jiang and Xiyun Yan

Nano Research, 2025, 18, 94907983
DOI: 10.26599/NR.2025.94907983

A Comprehensive Overview of Small-Molecule Androgen Receptor Degraders: Recent Progress and Future Perspectives

Si Ha, Guoshun Luo and Hua Xiang

J. Med. Chem., 2022, 65, 16128
DOI: 10.1021/acs.jmedchem.2c01487

Rational Design, Synthesis, and Biological Evaluation of Novel c-Met Degraders for Lung Cancer Therapy

Xingyang Qiu, Qingquan Zheng, Dongdong Luo, Yue Ming, Tingting Zhang, Wenchen Pu, Min Ai, Jianhua He and Yong Peng

J. Med. Chem., 2025, 68, 2815
DOI: 10.1021/acs.jmedchem.4c02129

Primary Amine-Based Photoclick Chemistry: From Concept to Diverse Applications in Chemical Biology and Medicinal Chemistry

Hao Hu, Hui-Jun Nie and Xiao-Hua Chen

Acc. Chem. Res., 2025, 58, 1963
DOI: 10.1021/acs.accounts.5c00158

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

Advances of bioorthogonal coupling reactions in drug development

Feiyan Zhan, Jingjie Zhu, Shaowen Xie, Jinyi Xu and Shengtao Xu

European Journal of Medicinal Chemistry, 2023, 253, 115338
DOI: 10.1016/j.ejmech.2023.115338

DNA-Templated Spatially Controlled Proteolysis Targeting Chimera for Cyclin D1–CDK4/6 Complex Protein Degradation

Rong Zheng, Abhay Prasad, Deeksha Satyabola, Yang Xu, Subhajit Roy, Yichen Yan, Petr Šulc and Hao Yan

J. Am. Chem. Soc., 2025, 147, 29742
DOI: 10.1021/jacs.5c04918

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

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

Recent Advances in Nanomedicine: Cutting-Edge Research on Nano-PROTAC Delivery Systems for Cancer Therapy

Xiaoqing Wu, Yueli Shu, Yao Zheng, Peichuan Zhang, Hanwen Cong, Yingpei Zou, Hao Cai and Zhengyu Zha

Pharmaceutics, 2025, 17, 1037
DOI: 10.3390/pharmaceutics17081037

Correlation between Membrane Permeability and the Intracellular Degradation Activity of Proteolysis-Targeting Chimeras

Hidetomo Yokoo, Hinata Osawa, Kosuke Saito and Yosuke Demizu

Chem. Pharm. Bull., 2024, 72, 961
DOI: 10.1248/cpb.c24-00615

Development of PROTACs using computational approaches

Jingxuan Ge, Chang-Yu Hsieh, Meijing Fang, Huiyong Sun and Tingjun Hou

Trends in Pharmacological Sciences, 2024, 45, 1162
DOI: 10.1016/j.tips.2024.10.006

Liposomal STAT3-Degrading PROTAC Prodrugs Promote Anti-Hepatocellular Carcinoma Immunity via Chemically Reprogramming Cancer Stem Cells

Xuan Wang, Youbo Zhao, Xin Li, Qiqi Zhang, Jinming He, Yingqi Liu, Menghuan Li and Zhong Luo

Nano Lett., 2024
DOI: 10.1021/acs.nanolett.4c00201

Discovery of novel 20S proteasome subunit β5 PROTAC degraders as potential therapeutics for pharyngeal carcinoma and Bortezomib-resistant multiple myeloma

Shumei Wang, Zhenzhen Li, Siyue Ma, Shuxin Zhang, Shuxian Guo, Zhao Ma, Lupei Du and Minyong Li

Bioorganic Chemistry, 2024, 153, 107801
DOI: 10.1016/j.bioorg.2024.107801

Decoy-PROTAC for specific degradation of “Undruggable” STAT3 transcription factor

Shiqing Li, Xin Wang, Jiabao Huang, Xiuping Cao, Yana Liu, Shiyan Bai, Tao Zeng, Qi Chen, Chunsen Li, Chunhua Lu and Huanghao Yang

Cell Death Dis, 2025, 16
DOI: 10.1038/s41419-025-07535-x

Expanding the druggable proteome strategies and innovations in targeted protein degradation

Ke Ma, Ting Liu, Wen-Bo Huan, Ke-Zheng Chen and Sheng-Lin Qiao

Nano Today, 2026, 67, 102945
DOI: 10.1016/j.nantod.2025.102945

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

Spatiotemporally Controllable Covalent Bonding of RNA for Multi‐Protein Interference

Hao Fang, Tingting Wang, Jun Dai, Jing‐Jing Hu, Zhaojun Chen, Lizhen Yuan, Yuning Hong, Fan Xia and Xiaoding Lou

Adv Healthcare Materials, 2024, 13
DOI: 10.1002/adhm.202304108

Recent advances in targeted protein degraders as potential therapeutic agents

Na Yang, Bo Kong, Zhaohong Zhu, Fei Huang, Liliang Zhang, Tao Lu, Yadong Chen, Yanmin Zhang and Yulei Jiang

Mol Divers, 2024, 28, 309
DOI: 10.1007/s11030-023-10606-w

Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization

Martin P. Schwalm, Andreas Krämer, Anja Dölle, Janik Weckesser, Xufen Yu, Jian Jin, Krishna Saxena and Stefan Knapp

Cell Chemical Biology, 2023, 30, 753
DOI: 10.1016/j.chembiol.2023.06.002

Discovery of Potent SOS1 PROTACs with Effective Antitumor Activities against NCI-H358 Tumor Cells In Vitro/In Vivo

Xudong Pang, Dawei Cui, Binhua Lv and Cheng-Yun Wang

J. Med. Chem., 2024, 67, 1563
DOI: 10.1021/acs.jmedchem.3c02135

Targeted degradation of specific TEAD paralogs by small molecule degraders

Hui Chen, Artem Gridnev, Netanya Schlamowitz, Wanyi Hu, Kuntala Dey, Guangrong Zheng and Jyoti R. Misra

Heliyon, 2024, 10, e37829
DOI: 10.1016/j.heliyon.2024.e37829

Ginsenoside Rh2- functionalized liposomes enhanced BRD4-PROTAC delivery and antitumor efficacy via improved tumor targeting and ECM remodeling

Lijuan Wen, Jialei Rao, Jiaoting Chen, Fang Li, Xixi Chen, Shenpeng Guo, Binghui Cui, Caisheng Qiu and Weiliang Chen

Materials Today Bio, 2026, 36, 102767
DOI: 10.1016/j.mtbio.2026.102767

Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors

Haiting Duan, Jingyu Zhang, Renzhao Gui, Yang Lu, Ao Pang, Beijing Chen, Liteng Shen, Hengyuan Yu, Jia Li, Tengfei Xu, Yuwei Wang, Xiaojun Yao, Bo Zhang, Nengming Lin, Xiaowu Dong, Yubo Zhou and Jinxin Che

J. Med. Chem., 2024, 67, 11326
DOI: 10.1021/acs.jmedchem.4c00883

Targeting Metabolism: Innovative Therapies for MASLD Unveiled

Weixin Wang, Xin Gao, Wentong Niu, Jinping Yin and Kan He

IJMS, 2025, 26, 4077
DOI: 10.3390/ijms26094077

DNA Tetrahedron-Driven Multivalent Proteolysis-Targeting Chimeras: Enhancing Protein Degradation Efficiency and Tumor Targeting

Shiqing Li, Tao Zeng, Zhixing Wu, Jiabao Huang, Xiuping Cao, Yana Liu, Shiyan Bai, Qi Chen, Chunsen Li, Chunhua Lu and Huanghao Yang

J. Am. Chem. Soc., 2025, 147, 2168
DOI: 10.1021/jacs.4c16438

A comprehensive primer and review of PROTACs and their In Silico design

Jacopo Zattoni, Paola Vottero, Gea Carena, Chiara Uliveto, Giulia Pozzati, Benedetta Morabito, Ebenezea Gitari, Jack Tuszynski and Maral Aminpour

Computer Methods and Programs in Biomedicine, 2025, 264, 108687
DOI: 10.1016/j.cmpb.2025.108687

Selective degradation of the p53‐R175H oncogenic hotspot mutant by an RNA aptamer‐based PROTAC

Lingping Kong, Fanlu Meng, Sijin Wu, Ping Zhou, Ruixin Ge, Min Liu, Linlin Zhang, Jun Zhou, Diansheng Zhong and Songbo Xie

Clinical & Translational Med, 2023, 13
DOI: 10.1002/ctm2.1191

Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer

Yaxun Guo, Yuzhan Li, Zhongmei Zhou, Lei Hou, Wenjing Liu, Wenlong Ren, Dazhao Mi, Jian Sun, Xueqin Dai, Yingying Wu, Zhuo Cheng, Tingyue Wu, Qianmei Luo, Cong Tian, Fubing Li, Zhigang Yu, Yihua Chen and Ceshi Chen

J Exp Clin Cancer Res, 2024, 43
DOI: 10.1186/s13046-024-03237-y

PROTAC-DB 3.0: an updated database of PROTACs with extended pharmacokinetic parameters

Jingxuan Ge, Shimeng Li, Gaoqi Weng, Huating Wang, Meijing Fang, Huiyong Sun, Yafeng Deng, Chang- Yu Hsieh, Dan Li and Tingjun Hou

Nucleic Acids Research, 2025, 53, D1510
DOI: 10.1093/nar/gkae768

Application of PROTACs in target identification and validation

Yang Liu, Jing Liang, Rui Zhu, Yueying Yang, Yali Wang, Wenyi Wei, Hua Li and Lixia Chen

Acta Materia Medica, 2024, 3
DOI: 10.15212/AMM-2024-0010

The application of PROTACs in immune-inflammation diseases

Chao Zhang, Xiuyun Sun, Peilu Song and Yu Rao

Bioorganic & Medicinal Chemistry, 2024, 115, 117967
DOI: 10.1016/j.bmc.2024.117967

Nano Proteolysis Targeting Chimeras (PROTACs) with Anti‐Hook Effect for Tumor Therapy

Ni‐Yuan Zhang, Da‐Yong Hou, Xing‐Jie Hu, Jian‐Xiao Liang, Man‐Di Wang, Zhang‐Zhi Song, Li Yi, Zhi‐Jia Wang, Hong‐Wei An, Wanhai Xu and Hao Wang

Angewandte Chemie, 2023, 135
DOI: 10.1002/ange.202308049

Modular Assembly of Heterotrifunctional Molecules Enabled by Iodosulfonylation of Allenes and Subsequent Amination

Xiaofeng Lin, Chuxiong Peng, Shijie Liu, Jianpin Xiang, Binyan Lin, Qichen Zhan, Peng Cao and Tao Cao

J. Med. Chem., 2024, 67, 21251
DOI: 10.1021/acs.jmedchem.4c02114

Enzyme‐Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment‐Responsive Immunomodulation

Caixia Sun, Songhan Liu, Jun Wei Lau, Hanyu Yang, Yun Chen and Bengang Xing

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202423057

Single amino acid–based PROTACs trigger degradation of the oncogenic kinase BCR–ABL in chronic myeloid leukemia (CML)

Jianchao Zhang, Caibing Ma, Yongjun Yu, Chaowei Liu, Lijing Fang and Hai Rao

Journal of Biological Chemistry, 2023, 299, 104994
DOI: 10.1016/j.jbc.2023.104994

Facile Synthesis of Homodimeric Protein Ligands

Weijun Gui and Thomas Kodadek

ChemBioChem, 2023, 24
DOI: 10.1002/cbic.202300392

Targeting Arginine Methyltransferase PRMT5 for Cancer Therapy: Updated Progress and Novel Strategies

Jiahong Zheng, Bang Li, Yingqi Wu, Xiaoshuang Wu and Yuanxiang Wang

J. Med. Chem., 2023, 66, 8407
DOI: 10.1021/acs.jmedchem.3c00250

In silico modeling of targeted protein degradation

Wenxing Lv, Xiaojuan Jia, Bowen Tang, Chao Ma, Xiaopeng Fan, Xurui Jin, Zhangming Niu and Xin Han

European Journal of Medicinal Chemistry, 2025, 289, 117432
DOI: 10.1016/j.ejmech.2025.117432

Multi-Faceted Roles of DNAJB Protein in Cancer Metastasis and Clinical Implications

Hye-Youn Kim and Suntaek Hong

IJMS, 2022, 23, 14970
DOI: 10.3390/ijms232314970

Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma

Jinbo Huang, Jiajie Su, Haiyu Wang, Jiayi Chen, Yuan Tian, Jun Zhang, Tingting Feng, Longjiang Di, Xiaopeng Lu, Hao Sheng, Qian Zhu, Xinyun Chen, Jingchao Wang, Xingkai He, Yerkezhan Yerkinkazhina, Zhongyi Xie, Yuxin Shu, Tianshu Kang, Huangqi Tang, Jinqin Qian and Wei-Guo Zhu

J. Med. Chem., 2024, 67, 17319
DOI: 10.1021/acs.jmedchem.4c01223

DDR1-targeted therapies: current limitations and future potential

Donglin Wu, Zihui Ding, Tao Lu, Yadong Chen, Feng Zhang and Shuai Lu

Drug Discovery Today, 2024, 29, 103975
DOI: 10.1016/j.drudis.2024.103975

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies

Xiaopeng Peng, Zhihao Hu, Limei Zeng, Meizhu Zhang, Congcong Xu, Benyan Lu, Chengpeng Tao, Weiming Chen, Wen Hou, Kui Cheng, Huichang Bi, Wanyi Pan and Jianjun Chen

Acta Pharmaceutica Sinica B, 2024, 14, 533
DOI: 10.1016/j.apsb.2023.09.003

Targeted Protein Degradation Induced by HEMTACs Based on HSP90

Zhenzhen Li, Siyue Ma, Ling Zhang, Shuxin Zhang, Zhao Ma, Lupei Du and Minyong Li

J. Med. Chem., 2023, 66, 733
DOI: 10.1021/acs.jmedchem.2c01648

Synthesis and degradation effect of PROTACs targeting EGFR triple mutants

Xiao-Xiao Xi, Hong-Yi Zhao, Minhang Xin, Shuai Mao and San-Qi Zhang

Bioorganic & Medicinal Chemistry, 2026, 132, 118427
DOI: 10.1016/j.bmc.2025.118427

Peptide-Mediated Small Molecule Lysosome-Targeting Chimeras for Targeted Degradation of Membrane and Intracellular Proteins

Shuqiang Chen, Wei Wang, Zhipeng Chen, Ruyan Li, Zhe Wu, Guoqiang Dong and Chunquan Sheng

J. Med. Chem., 2024, 67, 15807
DOI: 10.1021/acs.jmedchem.4c01449

PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens

Alessandro Bazzacco, Beatrice Mercorelli, Arianna Loregian and Christian Münz

FEMS Microbiology Reviews, 2025, 49
DOI: 10.1093/femsre/fuaf046

Synthesis and anticancer activity of parthenolide-based PROTACs for IKKβ degradation

Zhenxi Su, Yiwu Wu, Yijie Su, Yuhan He, Jieyin Liu and Deng-Gao Zhao

Bioorganic & Medicinal Chemistry Letters, 2026, 135, 130571
DOI: 10.1016/j.bmcl.2026.130571

Leveraging chemotherapy-induced PD-L1 upregulation to potentiate targeted PD-L1 degradation using nanoparticle-based targeting chimeras

Yuai Li, Jingwen Wang, Ruilian Yu, Tao Gong, Zhirong Zhang, Renhe Liu and Yao Fu

Chemical Engineering Journal, 2024, 499, 155708
DOI: 10.1016/j.cej.2024.155708

Annual review of PROTAC degraders as anticancer agents in 2022

Xiao Wang, Zhao-Long Qin, Na Li, Mei-Qi Jia, Qiu-Ge Liu, Yi-Ru Bai, Jian Song, Shuo Yuan and Sai-Yang Zhang

European Journal of Medicinal Chemistry, 2024, 267, 116166
DOI: 10.1016/j.ejmech.2024.116166

A breast cancer targeted photodynamic degrader to activate immunotherapy through EGFR degradation mediated PD-L1 downregulation

Yuxuan Wei, Zuxiao Chen, Chuyu Huang, Hong Cheng, Xiaofeng Jiang and Shiying Li

Chemical Engineering Journal, 2024, 488, 150822
DOI: 10.1016/j.cej.2024.150822

Integrating PROTAC-based targeted protein degradation with nanodelivery systems to overcome cancer therapeutic resistance

Xinyu Gou, Shi He, Bilan Wang, Lingli Zhang, Yongzhong Cheng and Xiang Gao

Advanced Drug Delivery Reviews, 2026, 229, 115755
DOI: 10.1016/j.addr.2025.115755

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

A Keap1-recruiting BRD4 degrader offers a single-molecular polypharmacology approach for the treatment of metabolic dysfunction-associated steatohepatitis

Xian Zhang, Yuxin Ge, Mengjie Ye, Xiaolu Wang, Yuanyuan Tong, Chihong Liu, Shicheng Xu, Ziquan Zhao, Qidong You, Xiaoke Guo and Zhengyu Jiang

Free Radical Biology and Medicine, 2025, 232, 15
DOI: 10.1016/j.freeradbiomed.2025.02.042

Recent advances of targeting nicotinamide phosphoribosyltransferase (NAMPT) for cancer drug discovery

He Tang, Lin Wang, Tianyu Wang, Jiamei Yang, Shuai Zheng, Jun Tong, Sheng Jiang, Xiangyu Zhang and Kuojun Zhang

European Journal of Medicinal Chemistry, 2023, 258, 115607
DOI: 10.1016/j.ejmech.2023.115607

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

Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Xin Xie, Tingting Yu, Xiang Li, Nan Zhang, Leonard J. Foster, Cheng Peng, Wei Huang and Gu He

Sig Transduct Target Ther, 2023, 8
DOI: 10.1038/s41392-023-01589-z

Current advances and development strategies of orally bioavailable PROTACs

Shenxin Zeng, Yingqiao Ye, Heye Xia, Jingli Min, Jiamei Xu, Zunyuan Wang, Youlu Pan, Xinglu Zhou and Wenhai Huang

European Journal of Medicinal Chemistry, 2023, 261, 115793
DOI: 10.1016/j.ejmech.2023.115793

Modulating Phosphorylation by Proximity-Inducing Modalities for Cancer Therapy

Qiuyue Zhang, Jia Yu, Qidong You and Lei Wang

J. Med. Chem., 2024, 67, 21695
DOI: 10.1021/acs.jmedchem.4c02624

Rational modification of PROTACs for tumor-selective protein degradation

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

Advanced Drug Delivery Reviews, 2026, 230, 115775
DOI: 10.1016/j.addr.2026.115775

Identification of Actionable Targeted Protein Degradation Effector Sites through Site-Specific Ligand Incorporation-Induced Proximity (SLIP)

Zhangping Xiao, Efthymios S. Gavriil, Fangyuan Cao, Xinyue Zhang, Stan Xiaogang Li, Sergei Kotelnikov, Patrycja Michalska, Friederike Marte, Chloe Huang, Yudi Lu, Yunxuan Zhang, Erika Bernardini, Dima Kozakov and Edward W. Tate

J. Am. Chem. Soc., 2025, 147, 21549
DOI: 10.1021/jacs.5c01420

Design and Synthesis of Pyrrolo[3,4-d]pyrimidine-Based ATR Degraders for Effective Treatment of Colorectal Cancer in Mouse Model

Nian-Dong Mao, Zi Hui, Chen-Chen Wang, Meng-Lan He, Shun-Ran Li, Meng-Qian Yu, Lulu Ye, Jia-Wei Zhou, Zong-Hao Wang, Bo-Qun Du, Guo-Wei Ye, Yu-Qing Zhang, Xia Yao, Xing-Lin Feng, Frédéric Lirussi, Carmen Garrido, Yuan Gao, Hui Luo and Xiang-Yang Ye

J. Med. Chem., 2026, 69, 6902
DOI: 10.1021/acs.jmedchem.5c03155

In Vivo Self‐Assembly of PROTACs by Bioorthogonal Chemistry for Precision Cancer Therapy

Shaowen Xie, Jingjie Zhu, Yihan Peng, Fangyi Zhan, Feiyan Zhan, Chen He, Dazhi Feng, Jia Xie, Jingyu Liu, Huajian Zhu, Hong Yao, Jinyi Xu, Zhigui Su and Shengtao Xu

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202421713

Characteristic roadmap of linker governs the rational design of PROTACs

Yawen Dong, Tingting Ma, Ting Xu, Zhangyan Feng, Yonggui Li, Lingling Song, Xiaojun Yao, Charles R. Ashby and Ge-Fei Hao

Acta Pharmaceutica Sinica B, 2024, 14, 4266
DOI: 10.1016/j.apsb.2024.04.007

A long march for targeted protein degradation in the new era: expanding E3 ligases

Dazhao Mi, Anxin Huang, Jingfeng Song and Yihua Chen

Future Medicinal Chemistry, 2024, 16, 2189
DOI: 10.1080/17568919.2024.2409618

A Peptide-Based PROTAC Degrader of BRCA2 Sensitizes Metastatic Castration-Resistant Prostate Cancer to PARP Inhibition

Qi Ye, Bohan Ma, Lei Li, Zixi Wang, Mingming Lu, Jialu Kang, Yuzeshi Lei, Shan Xu, Ke Wang, Yanlin Jian, Yizeng Fan, Bin Wang, Jing Liu, Yang Gao, Jian Ma and Lei Li

Cancer Research, 2025, 85, 3490
DOI: 10.1158/0008-5472.CAN-24-4096

Proteolysis-Targeting Chimeras (PROTACs) targeting the BCR-ABL for the treatment of chronic myeloid leukemia – a patent review

André T. S. Vicente and Jorge A.R. Salvador

Expert Opinion on Therapeutic Patents, 2023, 33, 397
DOI: 10.1080/13543776.2023.2240025

Harnessing the Power of Natural Products for Targeted Protein Degradation

Bo Zhu, Zheng Wu, Yiwen Shou, Kaili Zhao, Qinpei Lu, Jiang‐Jiang Qin and Hongwei Guo

Medicinal Research Reviews, 2025, 45, 1466
DOI: 10.1002/med.22113

Continuous Flow Synthesis of Amides in Bio-Derived Solvent GVL

Xu-Yang Mu, Rui Zhu, Li-Jie Yu and Wen-Long Wang

LOC, 2025, 22, 194
DOI: 10.2174/0115701786313379240815113722

Amphiphilic Affibody-PROTAC conjugate Self-Assembled nanoagents for targeted cancer therapy

Wenhui Gao, Xuelin Xia, Xiaoyuan Yang, Qingrong Li, Xiaoxia Xia, Wei Huang and Deyue Yan

Chemical Engineering Journal, 2024, 495, 153437
DOI: 10.1016/j.cej.2024.153437

Targeting kelch-like (KLHL) proteins: achievements, challenges and perspectives

Yangguo Zhou, Qiong Zhang, Ziquan Zhao, Xiuqi Hu, Qidong You and Zhengyu Jiang

European Journal of Medicinal Chemistry, 2024, 269, 116270
DOI: 10.1016/j.ejmech.2024.116270

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

Discovery of Potent and Highly Selective Interleukin-2-Inducible T-Cell Kinase Degraders with In Vivo Activity

Danli Zhou, Yingying Zuo and Zhengying Pan

J. Med. Chem., 2023, 66, 4979
DOI: 10.1021/acs.jmedchem.2c02078

Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype

Gang Xue, Jianing Xie, Matthias Hinterndorfer, Marko Cigler, Lara Dötsch, Hana Imrichova, Philipp Lampe, Xiufen Cheng, Soheila Rezaei Adariani, Georg E. Winter and Herbert Waldmann

Nat Commun, 2023, 14
DOI: 10.1038/s41467-023-43657-6

Development of a GC-376 Based Peptidomimetic PROTAC as a Degrader of 3-Chymotrypsin-like Protease of SARS-CoV-2

Deborah Grifagni, Elena Lenci, Alessia De Santis, Andrea Orsetti, Carlo Giorgio Barracchia, Filomena Tedesco, Raffaele Bellini Puglielli, Francesca Lucarelli, Angela Lauriola, Michael Assfalg, Francesca Cantini, Vito Calderone, Daniele Guardavaccaro, Andrea Trabocchi, Mariapina D’Onofrio and Simone Ciofi-Baffoni

ACS Med. Chem. Lett., 2024, 15, 250
DOI: 10.1021/acsmedchemlett.3c00498

Discovery of the First Potent, Selective, and In Vivo Efficacious Polo-like Kinase 4 Proteolysis Targeting Chimera Degrader for the Treatment of TRIM37-Amplified Breast Cancer

Yin Sun, Yanli Xue, Pengkun Sun, Shuyi Mu, Hongbing Liu, Yu Sun, Lin Wang, Jingkai Wang, Tianxiao Wu, Wenbo Yin, Qiaohua Qin, Yixiang Sun, Nian Liu, Hanxun Wang, Huali Yang, Dongmei Zhao and Maosheng Cheng

J. Med. Chem., 2023, 66, 8200
DOI: 10.1021/acs.jmedchem.3c00505

Versatile One-Pot Synthesis of Hydrophobic Tags by Multicomponent Reactions

Federica Carolina Balestrero, Laura Gioiello, Georgia Goutsiou, Sabina Sangaletti, Rita Maria Concetta Di Martino, Fabrizio Condorelli, Ambra A. Grolla and Tracey Pirali

ACS Omega, 2025, 10, 4745
DOI: 10.1021/acsomega.4c09726

Advancing Design Strategy of PROTACs for Cancer Therapy

Hang Luo, Yuan Tian, Razack Abdullah, Baoting Zhang, Yuan Ma and Ge Zhang

MedComm, 2025, 6
DOI: 10.1002/mco2.70258

Enhancing therapeutic efficacy in homologous recombination-proficient pancreatic cancer via the combination of PARP1-PROTAC and a BRD4 inhibitor

Chunlan Pu, Yuanyuan Liu, Suke Lan, Hengrui Fan, Lvye Liu, Jianyu Liu and Yuanbiao Guo

Bioorganic & Medicinal Chemistry, 2024, 115, 117970
DOI: 10.1016/j.bmc.2024.117970

Mighty mini-PROTACs: an emerging class of degraders

Xiao Chen, Kefan Liao, Jiawei Yuan, Jianchao Zhang and Hai Rao

European Journal of Medicinal Chemistry, 2026, 301, 118202
DOI: 10.1016/j.ejmech.2025.118202

Degradation of Cyclin-Dependent Kinase: A New Weapon for Cancer Therapy

Xing Tian, Xiaojie Dai, Ye Zhong, Maosheng Cheng and Yang Liu

Pharmaceutical Fronts, 2025, 07, e275
DOI: 10.1055/a-2742-7859

RIPTACs: A groundbreaking approach to drug discovery

Zonghui Ma, Andrew A. Bolinger and Jia Zhou

Drug Discovery Today, 2023, 28, 103774
DOI: 10.1016/j.drudis.2023.103774

Unveiling a new strategy for PDIA1 inhibition: Integration of activity-based probes profiling and targeted degradation

Bei Zhang, Dawei Hong, Hujuan Qian, Keqing Ma, Liquan Zhu, Linye Jiang and Jingyan Ge

Bioorganic Chemistry, 2024, 150, 107585
DOI: 10.1016/j.bioorg.2024.107585

Exploiting E3 ligases for lung cancer therapy: The promise of DCAF-PROTACs

Md Sadique Hussain, Lina Eltaib, Amita Joshi Rana, Mudasir Maqbool, Sumel Ashique, Mashael N. Alanazi, Yumna Khan and Mohit Agrawal

Pathology - Research and Practice, 2025, 270, 156001
DOI: 10.1016/j.prp.2025.156001

PROTAC^® technology and potential for its application in infection control

M. A. Zakharova and M. V. Chudinov

Fine Chem. Technol., 2024, 19, 214
DOI: 10.32362/2410-6593-2024-19-3-214-231

RIPTACs for Precision Cancer Therapy: A Novel Modality with the Inspiration of HLD-0915 as the First Candidate in Clinical Trials

Zonghui Ma, Cun Zhang, Qiang Shen and Jia Zhou

J. Med. Chem., 2025, 68, 10503
DOI: 10.1021/acs.jmedchem.5c01250

Senolysis Enabled by Senescent Cell‐Sensitive Bioorthogonal Tetrazine Ligation

Mengyang Chang, Yue Dong, Hang Xu, Alexis B. Cruickshank‐Taylor, Jacob S. Kozora, Baran Behpour and Wei Wang

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202315425

Selective Elimination of Senescent Cancer Cells by Galacto-Modified PROTACs

Mengyang Chang, Feng Gao, Giri Gnawali, Hang Xu, Yue Dong, Xiang Meng, Wenpan Li, Zhiren Wang, Byrdie Lopez, Jennifer S. Carew, Steffan T. Nawrocki, Jianqin Lu, Qing-Yu Zhang and Wei Wang

J. Med. Chem., 2024, 67, 7301
DOI: 10.1021/acs.jmedchem.4c00152

Split‐Deliver‐Click: Tumor‐Specific Protein Degradation via “AND” Logic‐Gated In‐Cell Bioorthogonal Clicking of PROTACs

He Dong, Cilong Chu, Ihsan Ullah, Qing Xu, Zhenhai Pan and Youyong Yuan

Angew Chem Int Ed, 2026, 65
DOI: 10.1002/anie.202520774

Degradation of Hexokinase 2 Blocks Glycolysis and Induces GSDME-Dependent Pyroptosis to Amplify Immunogenic Cell Death for Breast Cancer Therapy

Ruoxi Sang, Renming Fan, Aohua Deng, Jiakui Gou, Ruizhuo Lin, Ting Zhao, Yongrui Hai, Junke Song, Yang Liu, Bing Qi, Guanhua Du, Maosheng Cheng and Gaofei Wei

J. Med. Chem., 2023, 66, 8464
DOI: 10.1021/acs.jmedchem.3c00118

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

N-deglycosylation targeting chimera (DGlyTAC): a strategy for immune checkpoint proteins inactivation by specifically removing N-glycan

Li Li, Jiajia Wu, Weiqian Cao, Wei Zhang, Qi Wu, Yaxu Li, Yanrong Yang, Zezhi Shan, Zening Zheng, Xin Ge, Liang Lin and Ping Wang

Sig Transduct Target Ther, 2025, 10
DOI: 10.1038/s41392-025-02219-6

Research in the Field of Drug Design and Development

Grazyna Biala, Ewa Kedzierska, Marta Kruk-Slomka, Jolanta Orzelska-Gorka, Sara Hmaidan, Aleksandra Skrok, Jakub Kaminski, Eva Havrankova, Dominika Nadaska and Ivan Malik

Pharmaceuticals, 2023, 16, 1283
DOI: 10.3390/ph16091283

Enzyme‐Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment‐Responsive Immunomodulation

Caixia Sun, Songhan Liu, Jun Wei Lau, Hanyu Yang, Yun Chen and Bengang Xing

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202423057

Design, synthesis, and biological evaluation of novel PROTACs based on unnatural dipeptide CRBN ligands

Kun Huang, Peng Luo, Cai-Hua Li, Nan Huang, Kun Yao, Xiong-Xiong Lan, Ling-Feng Du, Yan Miao, Qing Tang, Ying Xu, Yong-Xia Zhu and Ning-Yu Wang

European Journal of Medicinal Chemistry, 2026, 303, 118387
DOI: 10.1016/j.ejmech.2025.118387

ClickRNA-PROTAC for Tumor-Selective Protein Degradation and Targeted Cancer Therapy

Xucong Teng, Xuan Zhao, Yicong Dai, Xiangdong Zhang, Qiushuang Zhang, Yuncong Wu, Difei Hu and Jinghong Li

J. Am. Chem. Soc., 2024, 146, 27382
DOI: 10.1021/jacs.4c06402

Photo-Activated PROTACs for Targeted BRD4 Degradation and Synergistic Photodynamic Therapy in Bladder Cancer

Ke Wang, Mingzhu Zhang, Cheng Huang, Jishuang Zhang, Yinan Hua, Xinlu Qin, Yongming Deng, Shaohua Wei and Lin Zhou

Mol. Pharmaceutics, 2025, 22, 3388
DOI: 10.1021/acs.molpharmaceut.5c00271

Discovery and Characterization of RP03707: A Highly Potent and Selective KRASG12D PROTAC

Xiang Ji, Huanping Li, Gang Wu, Qiguo Zhang, Xiaolin He, Yanpeng Wu, Bin Zong, Xiaojin Xu, Chao Liang, Beibei Wang, Yuwei Zhang, Qingyao Hu, Chao Deng, Liqiang Shen, Zijun Chen, Bing Bai, Lin Wang, Jinchao Ai, Leduo Zhang, Honggui Zhou, Shihao Sun, Yijie Wang, Youhong Wang, Qiming Fan, Dawei Chen, Tianlun Zhou, Xianqi Kong and Jiasheng Lu

J. Med. Chem., 2025, 68, 10238
DOI: 10.1021/acs.jmedchem.5c00428

Design, synthesis, and biological evaluation of RIPK1-targeting PROTACs

Hefeng Zhang, Shuonan Zhang, Tianchen Wang, Yaohan Lan, Yang Dai, Xia Peng, Yuxiang An, Yi Xue, Jing Ai and Wenhu Duan

Mol Divers, 2026, 30, 353
DOI: 10.1007/s11030-025-11166-x

Novel technologies are turning a dream into reality: conditionally replicating viruses as vaccines

Yan-Dong Tang, Changqing Yu and Xue-Hui Cai

Trends in Microbiology, 2024, 32, 292
DOI: 10.1016/j.tim.2023.09.002

High‐Throughput Miniaturized Synthesis of PROTAC‐Like Molecules

Ye Tian, Maximilian Seifermann, Liana Bauer, Charlotte Luchena, Janne J. Wiedmann, Stefan Schmidt, Alexander Geisel, Sergii Afonin, Julius Höpfner, Marius Brehm, Xinyong Liu, Carsten Hopf, Anna A. Popova and Pavel A. Levkin

Small, 2024, 20
DOI: 10.1002/smll.202307215

Solid‐Phase Parallel Synthesis of Photocleavable Bifunctional Molecules Enables Efficient Phenotypic Protein Degrader Discovery

Baoli Ding, Jiawen Hu, Rongtian Zhang, Binyan Shou, Mengdie Chen, Li Jiang, Meng Yuan, Bo Yang, Qiaojun He, Ji Cao and Cheng‐Liang Zhu

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202424118

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

Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase

Yangyang Chen, Yang Li, Jing Gao, Quanwei Yu, Yiwen Zhang and Jifa Zhang

European Journal of Medicinal Chemistry, 2024, 271, 116437
DOI: 10.1016/j.ejmech.2024.116437

PROTAC-based protein degradation: a window of opportunity for melanoma therapy

Giulia Gentile, Simona D’Aguanno, Marta Di Martile, Adele Petricca, Elisabetta Valentini, Stefano Scalera and Donatella Del Bufalo

J Biomed Sci, 2026, 33
DOI: 10.1186/s12929-026-01225-2

Discovery of Potent and Selective c-Met Degraders for Hepatocellular Carcinoma Treatment

Wenjian Min, Huanaoyu Yang, Dawei Wang, Chunling Chen, Yanyin Wang, Yi Hou, Yasheng Zhu, Chengliang Sun, Xiao Wang, Kai Yuan and Peng Yang

J. Med. Chem., 2024, 67, 12314
DOI: 10.1021/acs.jmedchem.4c01004

Structure-Based Design of “Head-to-Tail” Macrocyclic PROTACs

Chungen Li, Yihan Chen, Weixue Huang, Yudi Qiu, Shengjie Huang, Yang Zhou, Fengtao Zhou, Jian Xu, Xiaomei Ren, Jinwei Zhang, Zhen Wang, Ming Ding and Ke Ding

JACS Au, 2024, 4, 4866
DOI: 10.1021/jacsau.4c00831

Facilitating the development of molecular glues: Opportunities from serendipity and rational design

Weiqing Jiang, Yunhan Jiang, Youfu Luo, Wenliang Qiao and Tao Yang

European Journal of Medicinal Chemistry, 2024, 263, 115950
DOI: 10.1016/j.ejmech.2023.115950

Advancing Proteolysis Targeting Chimera (PROTAC) Nanotechnology in Protein Homeostasis Reprograming for Disease Treatment

Mengyao Wu, Yilan Zhao, Chi Zhang and Kanyi Pu

ACS Nano, 2024, 18, 28502
DOI: 10.1021/acsnano.4c09800