Synthesis and biological studies on ovarian cancer cells of new heterocyclic molecules inspired by MIM1, an inhibitor of the anti-apoptotic protein Mcl-1

Jocelyn Pezeril, Louis-Bastien Weiswald, Ali Soulieman, Hippolyte Paysant, Ali Hachem, Emilie Brotin, Christophe Denoyelle, Anne-Sophie Voisin-Chiret, Nicolas Gouault, René Grée, Nicolas Levoin and Laurent Poulain

New J. Chem., 2025, 49, 12688
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Discovery of histone deacetylase 3 (HDAC3)-specific PROTACs

Yufeng Xiao, Jia Wang, Lisa Y. Zhao, Xinyi Chen, Guangrong Zheng, Xuan Zhang and Daiqing Liao

Chem. Commun., 2020, 56, 9866
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Discovery of PZ671, a highly potent and in vivo active CRBN-recruiting Bcl-xL degrader

Peiyi Zhang, Dinesh Thummuri, Wanyi Hu, Sajid Khan, Yonghan He, Xuan Zhang, Pratik Pal, Dongwen Lv, Daohong Zhou and Guangrong Zheng

RSC Med. Chem., 2025, 16, 3495
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Target and tissue selectivity of PROTAC degraders

Robert G. Guenette, Seung Wook Yang, Jaeki Min, Baikang Pei and Patrick Ryan Potts

Chem. Soc. Rev., 2022, 51, 5740
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Cereblon: promise and challenges for combating human diseases

Hyoung Kyu Kim, Jung Eun Seol, Sang Woo Ahn, Seungje Jeon, Chul-Seung Park and Jin Han

Pflugers Arch - Eur J Physiol, 2021, 473, 1695
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Patent landscape of inhibitors and PROTACs of the anti-apoptotic BCL-2 family proteins

Pratik Pal, Peiyi Zhang, Saikat K. Poddar and Guangrong Zheng

Expert Opinion on Therapeutic Patents, 2022, 32, 1003
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PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics

Sajid Khan, Yonghan He, Xuan Zhang, Yaxia Yuan, Shaoyan Pu, Qingpeng Kong, Guangrong Zheng and Daohong Zhou

Oncogene, 2020, 39, 4909
DOI: 10.1038/s41388-020-1336-y

Design, Synthesis and In Vitro Investigation of Cabozantinib-Based PROTACs to Target c-Met Kinase

Anastasia A. Sachkova, Daria V. Andreeva, Alexander S. Tikhomirov, Alexander M. Scherbakov, Diana I. Salnikova, Danila V. Sorokin, Fedor B. Bogdanov, Yulia D. Rysina, Andrey E. Shchekotikhin, Ekaterina S. Shchegravina and Alexey Yu. Fedorov

Pharmaceutics, 2022, 14, 2829
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Design, Synthesis, and Evaluation of BCL‐2 Targeting PROTACs

Aleša Bricelj, Yuen Lam Dora Ng, Martina Gobec, Robert Kuchta, Wanyi Hu, Špela Javornik, Miha Rožič, Michael Gütschow, Guangrong Zheng, Jan Krönke, Christian Steinebach and Izidor Sosič

Chemistry A European J, 2024, 30
DOI: 10.1002/chem.202400430

Trends in targeting Bcl-2 anti-apoptotic proteins for cancer treatment

Zhenwei Zhang, Lijun Bai, Linghui Hou, Hongguang Deng, Shenglin Luan, Dan Liu, Min Huang and Linxiang Zhao

European Journal of Medicinal Chemistry, 2022, 232, 114184
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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
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Session 5: Protein Degraders

Kiran Palyada, Renee Hukkanen, Stephanie Leuenroth-Quinn, Allison Vitsky, Richard Peterson, Katie Stamp, Clare Hoover and Laurie Volak

Toxicol Pathol, 2024, 52, 553
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Selectivity through Targeted Protein Degradation (TPD)

Ariamala Gopalsamy

J. Med. Chem., 2022, 65, 8113
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PROTAC: An Effective Targeted Protein Degradation Strategy for Cancer Therapy

Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang and Jiang-Jiang Qin

Front. Pharmacol., 2021, 12
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Inhibiting the inhibitors: Targeting anti-apoptotic proteins in cancer and therapy resistance

Nir Shahar and Sarit Larisch

Drug Resistance Updates, 2020, 52, 100712
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Targeted protein degradation: advances in drug discovery and clinical practice

Guangcai Zhong, Xiaoyu Chang, Weilin Xie and Xiangxiang Zhou

Sig Transduct Target Ther, 2024, 9
DOI: 10.1038/s41392-024-02004-x

Novel selective strategies targeting the BCL-2 family to enhance clinical efficacy in ALK-rearranged non-small cell lung cancer

Fernando Martín, Clara Alcon, Elba Marín, Paula Morales-Sánchez, Albert Manzano-Muñoz, Sherley Díaz, Mireia García, Josep Samitier, Albert Lu, Alberto Villanueva, Noemí Reguart, Cristina Teixido and Joan Montero

Cell Death Dis, 2025, 16
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Discovery of Dual BCL-xL/BCL-w Degraders by Exploiting the Bis(sulfonyl)benzene Ring of ABT-263 as a Linkage Vector

Saikat K. Poddar, Yang Yang, Pratik Pal, Zeng Jin, Jing Pei, Yufeng Xiao, Wanyi Hu, Peiyi Zhang, Praise Adekunbi, Dinesh Thummuri, Yaxia Yuan, Dongwen Lv, J. Peter R. Pelletier, Weizhou Zhang, Daohong Zhou and Guangrong Zheng

J. Med. Chem., 2025, 68, 18684
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Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics

Joan Montero and Rizwan Haq

Cancer Discovery, 2022, 12, 1217
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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
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Direct Co-Targeting of Bcl-xL and Mcl-1 Exhibits Synergistic Effects in AR-V7–Expressing CRPC Models

Benjamin C. Brim, Andres F. Leon, Erica L. Beatson, Jessica D. Kindrick, Kinjal Bhadresha, Xiaohu Zhang, Giulia C. Napoli, Emily N. Risdon, Keith T. Schmidt, Kelli M. Wilson, Crystal McKnight, Erin Beck, Carleen Klumpp-Thomas, Michele Ceribelli, JuanJuan Yin, Adam G. Sowalsky, Douglas K. Price, Cindy H. Chau, Craig J. Thomas and William D. Figg

Cancer Research Communications, 2025, 5, 1396
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E3 ligase ligand optimization of Clinical PROTACs

Hanrui Jiang, Huan Xiong, Shuang-Xi Gu and Mingliang Wang

Front. Chem., 2023, 11
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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
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Recent Advances in PROTACs for Drug Targeted Protein Research

Tingting Yao, Heng Xiao, Hong Wang and Xiaowei Xu

IJMS, 2022, 23, 10328
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Developing PROteolysis TArgeting Chimeras (PROTACs) for hematologic malignancies

Yangping Wu, Jingliao Zhang, Xiaofan Zhu and Yingchi Zhang

Cancer Letters, 2022, 544, 215808
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Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

Shenxin Zeng, Wenhai Huang, Xiaoliang Zheng, Liyan cheng, Zhimin Zhang, Jian Wang and Zhengrong Shen

European Journal of Medicinal Chemistry, 2021, 210, 112981
DOI: 10.1016/j.ejmech.2020.112981

Can preclinical drug development help to predict adverse events in clinical trials?

Lap Hing Chi, Allan D. Burrows and Robin L. Anderson

Drug Discovery Today, 2022, 27, 257
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PROTACs to address the challenges facing small molecule inhibitors

Pedro Martín-Acosta and Xiangshu Xiao

European Journal of Medicinal Chemistry, 2021, 210, 112993
DOI: 10.1016/j.ejmech.2020.112993

Advances and perspectives of proteolysis targeting chimeras (PROTACs) in drug discovery

Jia-Yue Xi, Ru-Yue Zhang, Ke Chen, Lin Yao, Mu-Qiong Li, Ru Jiang, Xiao-Ye Li and Li Fan

Bioorganic Chemistry, 2022, 125, 105848
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PROTACs in platelets: emerging antithrombotic strategies and future perspectives

Justin S. Trory, Jordan Vautrinot, Carl J. May and Ingeborg Hers

Current Opinion in Hematology, 2025, 32, 34
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Chimera induced protein degradation: PROTACs and beyond

Lina Yin and Qingzhong Hu

European Journal of Medicinal Chemistry, 2020, 206, 112494
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Precision oncology revolution: CRISPR-Cas9 and PROTAC technologies unleashed

Karim Kanbar, Roy El Darzi and Diana E. Jaalouk

Front. Genet., 2024, 15
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Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-xL, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity

Xiaoyi Zhang, Yachuan Tao, Zhongli Xu, Biao Jiang, Xiaobao Yang, Taomin Huang and Wenfu Tan

Biochemical Pharmacology, 2024, 230, 116542
DOI: 10.1016/j.bcp.2024.116542

Structural Insights into PROTAC-Mediated Degradation of Bcl-xL

Chun-wa Chung, Han Dai, Esther Fernandez, Christopher P. Tinworth, Ian Churcher, Jenni Cryan, Jane Denyer, John D. Harling, Agnieszka Konopacka, Markus A. Queisser, Christopher J. Tame, Gillian Watt, Fan Jiang, Dongming Qian and Andrew B. Benowitz

ACS Chem. Biol., 2020, 15, 2316
DOI: 10.1021/acschembio.0c00266

Improved Accuracy for Modeling PROTAC-Mediated Ternary Complex Formation and Targeted Protein Degradation via New In Silico Methodologies

Michael L. Drummond, Andrew Henry, Huifang Li and Christopher I. Williams

J. Chem. Inf. Model., 2020, 60, 5234
DOI: 10.1021/acs.jcim.0c00897

Targeting Anti-Apoptotic BCL-2 Family Proteins for Cancer Treatment

Xuan Zhang, Xingui Liu, Daohong Zhou and Guangrong Zheng

Future Med. Chem., 2020, 12, 563
DOI: 10.4155/fmc-2020-0004

The path to venetoclax resistance is paved with mutations, metabolism, and more

Graeme P. Sullivan, Lyndsey Flanagan, Daniel Alencar Rodrigues and Tríona Ní Chonghaile

Sci. Transl. Med., 2022, 14
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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

Ehsan Gharib and Gilles A. Robichaud

IJMS, 2024, 25, 9463
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Cereblon-Recruiting PROTACs: Will New Drugs Have to Face Old Challenges?

Marcin Cieślak and Marta Słowianek

Pharmaceutics, 2023, 15, 812
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Assays and Technologies for Developing Proteolysis Targeting Chimera Degraders

Xingui Liu, Xuan Zhang, Dongwen Lv, Yaxia Yuan, Guangrong Zheng and Daohong Zhou

Future Med. Chem., 2020, 12, 1155
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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
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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

The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy

Meike Vogler, Yannick Braun, Victoria M. Smith, Mike-Andrew Westhoff, Raquel S. Pereira, Nadja M. Pieper, Marius Anders, Manon Callens, Tim Vervliet, Maha Abbas, Salvador Macip, Ralf Schmid, Geert Bultynck and Martin JS Dyer

Sig Transduct Target Ther, 2025, 10
DOI: 10.1038/s41392-025-02176-0

5-Oxo-hexahydroquinoline and 5-oxo-tetrahydrocyclopentapyridine derivatives as promising antiproliferative agents with potential apoptosis-inducing capacity

Sara Ranjbar, Mehdi Khoshneviszadeh, Marjan Tavakkoli, Ramin Miri, Najmeh Edraki and Omidreza Firuzi

Mol Divers, 2022, 26, 1481
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Targeted protein degradation: A promise for undruggable proteins

Kusal T.G. Samarasinghe and Craig M. Crews

Cell Chemical Biology, 2021, 28, 934
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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

PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors

Peiyi Zhang, Xuan Zhang, Xingui Liu, Sajid Khan, Daohong Zhou and Guangrong Zheng

Exploration of Targeted Anti-tumor Therapy, 2020, 1, 259
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The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs

Sarah T. Diepstraten, Mary Ann Anderson, Peter E. Czabotar, Guillaume Lessene, Andreas Strasser and Gemma L. Kelly

Nat Rev Cancer, 2022, 22, 45
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Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

Yonghan He, Sajid Khan, Zhiguang Huo, Dongwen Lv, Xuan Zhang, Xingui Liu, Yaxia Yuan, Robert Hromas, Mingjiang Xu, Guangrong Zheng and Daohong Zhou

J Hematol Oncol, 2020, 13
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Strategies to Reduce the On‐Target Platelet Toxicity of Bcl‐xL Inhibitors: PROTACs, SNIPERs and Prodrug‐Based Approaches

Arvind Negi and Anne Sophie Voisin‐Chiret

ChemBioChem, 2022, 23
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PROTAC targeted protein degraders: the past is prologue

Miklós Békés, David R. Langley and Craig M. Crews

Nat Rev Drug Discov, 2022, 21, 181
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Recent Advances in Small Molecular Modulators Targeting Histone Deacetylase 6

Yufeng Xiao and Xuan Zhang

Future Drug. Discov., 2020, 2
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PROTAC: A Novel Technology for Drug Development**

Jie Li and Jieqing Liu

ChemistrySelect, 2020, 5, 13232
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Discovery of XZ338, a highly potent BCL-XL degrader

Xuan Zhang, Dinesh Thummuri, Wanyi Hu, Xingui Liu, Peiyi Zhang, Shuo Zhou, Daohong Zhou and Guangrong Zheng

European Journal of Medicinal Chemistry, 2025, 291, 117624
DOI: 10.1016/j.ejmech.2025.117624

Recent advances in targeting protein degradation for tumor immunotherapy

Shuai Li, Yushan Jin, Huanhuan Wu, Hong Yuan and Jingyuan Zhao

J Hematol Oncol, 2025, 19
DOI: 10.1186/s13045-025-01765-4

Proteolysis-targeting chimeras (PROTACs) in cancer therapy

Xinyi Li, Wenchen Pu, Qingquan Zheng, Min Ai, Song Chen and Yong Peng

Mol Cancer, 2022, 21
DOI: 10.1186/s12943-021-01434-3

Targeted degradation of extracellular proteins: state of the art and diversity of degrader designs

M. A. A. Mamun, Anush G. Bakunts and Alexander L. Chernorudskiy

J Hematol Oncol, 2025, 18
DOI: 10.1186/s13045-025-01703-4

PROteolysis‐Targeting Chimeras (PROTACs) in leukemia: overview and future perspectives

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

MedComm, 2024, 5
DOI: 10.1002/mco2.575

The PROTAC selectively degrading BCL-XL inhibits the growth of tumors and significantly synergizes with Paclitaxel

Fenglan Qiu, Yachuan Tao, Yue Chen, Zhuqin Shen, Xuan Huang, Wenfu Tan, Taomin Huang and Xin Cao

Biochemical Pharmacology, 2025, 232, 116731
DOI: 10.1016/j.bcp.2024.116731

Small-Molecule PROTACs for Cancer Immunotherapy

Zefan Liu, Yajun Zhang, Yucheng Xiang and Xin Kang

Molecules, 2022, 27, 5439
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Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation

Zhihui Dou, Dapeng Zhao, Xiaohua Chen, Caipeng Xu, Xiaodong Jin, Xuetian Zhang, Yupei Wang, Xiaodong Xie, Qiang Li, Cuixia Di and Hong Zhang

J Exp Clin Cancer Res, 2021, 40
DOI: 10.1186/s13046-021-02001-w

Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity

Xuan Zhang, Dinesh Thummuri, Xingui Liu, Wanyi Hu, Peiyi Zhang, Sajid Khan, Yaxia Yuan, Daohong Zhou and Guangrong Zheng

European Journal of Medicinal Chemistry, 2020, 192, 112186
DOI: 10.1016/j.ejmech.2020.112186

E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities

Qiang Zou, Meng Liu, Kewei Liu, Yi Zhang, Brian J. North and Bin Wang

Cell Oncol., 2023, 46, 545
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The advancement of ubiquitination regulation in apoptosis, ferroptosis, autophagy, drug resistance and treatment of cancer

Hui Ling, Shuyao Xiao, Yalin Lei, Yujie Zhou, Jiaying Tan, Xiaojie Chen, Da Ma, Can Liang, Qingyi Liu, Wei Liu and Tiebing Zeng

Archives of Biochemistry and Biophysics, 2025, 771, 110497
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PROTAC as a novel anti-cancer strategy by targeting aging-related signaling

Yunhua Peng, Donghua Liu, Daoyuan Huang, Hiroyuki Inuzuka and Jing Liu

Seminars in Cancer Biology, 2024, 106-107, 143
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Current strategies for the design of PROTAC linkers: a critical review

Robert I. Troup, Charlene Fallan and Matthias G. J. Baud

Exploration of Targeted Anti-tumor Therapy, 2020, 1
DOI: 10.37349/etat.2020.00018

Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-XL and BCL-2

Michael J. Roy, Amelia Vom, Toru Okamoto, Brian J. Smith, Richard W. Birkinshaw, Hong Yang, Houda Abdo, Christine. A. White, David Segal, David C. S. Huang, Jonathan B. Baell, Peter M. Colman, Peter E. Czabotar and Guillaume Lessene

J. Med. Chem., 2021, 64, 5447
DOI: 10.1021/acs.jmedchem.0c01771

Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines

Xuan Zhang, Yonghan He, Peiyi Zhang, Vivekananda Budamagunta, Dongwen Lv, Dinesh Thummuri, Yang Yang, Jing Pei, Yaxia Yuan, Daohong Zhou and Guangrong Zheng

European Journal of Medicinal Chemistry, 2020, 199, 112397
DOI: 10.1016/j.ejmech.2020.112397

Ubiquitin recruiting chimera: more than just a PROTAC

Tatyana A. Grigoreva, Daria S. Novikova, Gerry Melino, Nick A. Barlev and Vyacheslav G. Tribulovich

Biol Direct, 2024, 19
DOI: 10.1186/s13062-024-00497-8

Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs

Shanique B. Alabi and Craig M. Crews

Journal of Biological Chemistry, 2021, 296, 100647
DOI: 10.1016/j.jbc.2021.100647

Discovery of Histone Deacetylase 8-Specific Proteolysis-Targeting Chimeras with Anticancer Activity against Hematological Malignancies

Shiyang Zhai, Marie Kemkes, Cindy-Esther Kponomaizoun, Jan Gerhartz, Felix Feller, Jia-Wey Tu, Dominika Ewa Pieńkowska, Julian Schliehe-Diecks, Ina Dressel, Michael Gütschow, Radosław P. Nowak, Christian Steinebach, Sanil Bhatia and Finn K. Hansen

J. Med. Chem., 2026, 69, 918
DOI: 10.1021/acs.jmedchem.5c00939

Recent Developments in Medicinal Chemistry and Therapeutic Potential of Anti-Cancer PROTACs-Based Molecules

Muhammad Zafar Irshad Khan, Adila Nazli, You-Lu Pan and Jian-Zhong Chen

CMC, 2023, 30, 1576
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Design and optimization of piperlongumine analogs as potent senolytics

Xuan Zhang, Yonghan He, Xingui Liu, Xin Zhang, Peizhong Shi, Yingying Wang, Daohong Zhou and Guangrong Zheng

Bioorganic & Medicinal Chemistry Letters, 2024, 98, 129593
DOI: 10.1016/j.bmcl.2023.129593