Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

Selective inhibition of BET bromodomains

Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262

Phthalimide conjugation as a strategy for in vivo target protein degradation

Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760

Catalytic in vivo protein knockdown by small-molecule PROTACs

Bondeson, D. P., Mares, A., Smith, I. E. D., Ko, E., Campos, S., Miah, A. H., Mulholland, K. E., Routly, N., Buckley, D. L., Gustafson, J. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1858 · Cited by 1,356

Structural basis of PROTAC cooperative recognition for selective protein degradation

Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242

Lysosome-targeting chimaeras for degradation of extracellular proteins

Banik, S. M., Pedram, K., Wisnovsky, S., Ahn, G., Riley, N. M., & Bertozzi, C. R. (2020) · Nature · doi:10.1038/s41586-020-2545-9 · Cited by 1,199

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

Zengerle, M., Chan, K.-H., & Ciulli, A. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00216 · Cited by 1,056

Lessons in PROTAC Design from Selective Degradation with a Promiscuous Warhead

Bondeson, D. P., Smith, B. E., Burslem, G. M., Buhimschi, A. D., Hines, J., Jaime-Figueroa, S., Wang, J., Hamman, B. D., Ishchenko, A., & Crews, C. M. (2018) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.010 · Cited by 923

Synthetic Multivalent Ligands as Probes of Signal Transduction

Kiessling, L. L., Gestwicki, J. E., & Strong, L. E. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200502794 · Cited by 864

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852

PROteolysis TArgeting Chimeras (PROTACs) — Past, present and future

Pettersson, M., & Crews, C. M. (2019) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2019.01.002 · Cited by 830

PROTACs: past, present and future

Li, K., & Crews, C. M. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00193d · Cited by 869

Lactate and lactylation in cancer

Chen, J., Huang, Z., Chen, Y., Tian, H., Chai, P., Shen, Y., Yao, Y., Xu, S., Ge, S., & Jia, R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02082-x · Cited by 545

Targeted protein degradation: from mechanisms to clinic

Tsai, J. M., Nowak, R. P., Ebert, B. L., & Fischer, E. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00729-9 · Cited by 438

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

Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396

Target and tissue selectivity of PROTAC degraders

Guenette, R. G., Yang, S. W., Min, J., Pei, B., & Potts, P. R. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00200k · Cited by 324

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

He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283

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

Diehl, C. J., & Ciulli, A. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00387b · Cited by 269

Targeted protein degradation for cancer therapy

Hinterndorfer, M., Spiteri, V. A., Ciulli, A., & Winter, G. E. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00817-8 · Cited by 263

Targeted protein degradation via intramolecular bivalent glues

Hsia, O., Hinterndorfer, M., Cowan, A. D., Iso, K., Ishida, T., Sundaramoorthy, R., Nakasone, M. A., Imrichova, H., Schätz, C., Rukavina, A., et al. (2024) · Nature · doi:10.1038/s41586-024-07089-6 · Cited by 222

Proximity-Based Modalities for Biology and Medicine

Liu, X., & Ciulli, A. (2023) · ACS Central Science · doi:10.1021/acscentsci.3c00395 · Cited by 206

Chasing molecular glue degraders: screening approaches

Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C., & Mayor-Ruiz, C. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00197g · Cited by 200

From Conception to Development: Investigating PROTACs Features for Improved Cell Permeability and Successful Protein Degradation

Cecchini, C., Pannilunghi, S., Tardy, S., & Scapozza, L. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.672267 · Cited by 201

Targeting cancer with small-molecule pan-KRAS degraders

Popow, J., Farnaby, W., Gollner, A., Kofink, C., Fischer, G., Wurm, M., Zollman, D., Wijaya, A., Mischerikow, N., Hasenoehrl, C., et al. (2024) · Science · doi:10.1126/science.adm8684 · Cited by 198

Discovery of XL01126: A Potent, Fast, Cooperative, Selective, Orally Bioavailable, and Blood–Brain Barrier Penetrant PROTAC Degrader of Leucine-Rich Repeat Kinase 2

Liu, X., Kalogeropulou, A. F., Domingos, S., Makukhin, N., Nirujogi, R. S., Singh, F., Shpiro, N., Saalfrank, A., Sammler, E. M., Ganley, I. G., et al. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c05499 · Cited by 201

PROTAC technology: A new drug design for chemical biology with many challenges in drug discovery

Guedeney, N., Cornu, M., Schwalen, F., Kieffer, C., & Voisin‐Chiret, A. S. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103395 · Cited by 180

Emerging degrader technologies engaging lysosomal pathways

Ding, Y., Xing, D., Fei, Y., & Lu, B. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00624c · Cited by 165

Intracellular Delivery of Glutathione Peroxidase Degrader Induces Ferroptosis In Vivo

Luo, T., Zheng, Q., Shao, L., Ma, T., Mao, L., & Wang, M. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202206277 · Cited by 136

A bibliometric analysis of PROTAC from 2001 to 2021

Li, D., Yu, D., Li, Y., & Yang, R. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114838 · Cited by 125

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

Zhang, N., Hou, D., Hu, X., Liang, J., Wang, M., Song, Z., Li, Y., Wang, Z., An, H., Xu, W., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202308049 · Cited by 117

Development of BromoTag: A “Bump-and-Hole”–PROTAC System to Induce Potent, Rapid, and Selective Degradation of Tagged Target Proteins

Bond, A. G., Craigon, C., Chan, K.-H., Testa, A., Karapetsas, A., Fasimoye, R. Y., Macartney, T., Blow, J. J., Alessi, D. R., & Ciulli, A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01532 · Cited by 116

Delivering on the promise of protein degraders

O’Brien, M. N., Luthra, S. A., Brown, M. F., & Bartlett, D. W. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00652-2 · Cited by 109

Aptamer-Based Targeted Protein Degradation

Liu, Y., Qian, X., Ran, C., Li, L., Fu, T., Su, D., Xie, S., & Tan, W. (2023) · ACS Nano · doi:10.1021/acsnano.2c10379 · Cited by 110

The importance of cellular degradation kinetics for understanding mechanisms in targeted protein degradation

Riching, K. M., Caine, E. A., Urh, M., & Daniels, D. L. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00339b · Cited by 108

Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy

Song, Y., Wang, S., Zhao, M., Yang, X., & Yu, B. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02008 · Cited by 101

Target protein localization and its impact on PROTAC-mediated degradation

Simpson, L. M., Glennie, L., Brewer, A., Zhao, J., Crooks, J., Shpiro, N., & Sapkota, G. P. (2022) · Cell chemical biology · doi:10.1016/j.chembiol.2022.08.004 · Cited by 106

Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy

Han, X., & Sun, Y. (2022) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2022.101062 · Cited by 89

Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs

Chen, N., Zhang, Z., Liu, X., Wang, H., Guo, R.-C., Wang, H., Hu, B., Shi, Y., Zhang, P., Liu, Z., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c00826 · Cited by 91

Targeted Biomolecule Regulation Platform: A Split-and-Mix PROTAC Approach

Yang, F., Luo, Q., Wang, Y., Liang, H., Wang, Y., Hou, Z., Wan, C., Wang, Y., Liu, Z., Ye, Y., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c12824 · Cited by 88

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

Peng, X., Hu, Z., Zeng, L., Zhang, M., Xu, C., Lu, B., Tao, C., Chen, W., Hou, W., Cheng, K., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.09.003 · Cited by 87

Hypoxia deactivates epigenetic feedbacks via enzyme-derived clicking proteolysis-targeting chimeras

Cong, T. D., Lau, J. W., Sun, C., Liu, S., Kha, T., Lim, S. T., Oon, Y. Y., Kwan, Y. P., Ma, J., Mu, Y., et al. (2022) · Science Advances · doi:10.1126/sciadv.abq2216 · Cited by 84

Mechanism of degrader-targeted protein ubiquitinability

Crowe, C., Nakasone, M. A., Chandler, S., Craigon, C., Sathe, G. J., Tatham, M. H., Makukhin, N., Hay, R. T., & Ciulli, A. (2024) · Science Advances · doi:10.1126/sciadv.ado6492 · Cited by 90

Recent Advances in PROTACs for Drug Targeted Protein Research

Yao, T., Xiao, H., Wang, H., & Xu, X. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810328 · Cited by 79

Protein Phosphatase 5-Recruiting Chimeras for Accelerating Apoptosis-Signal-Regulated Kinase 1 Dephosphorylation with Antiproliferative Activity

Zhang, Q., Wu, X., Zhang, H., Wu, Q., Fu, M., Hua, L., Zhu, X., Guo, Y., Zhang, L., You, Q., et al. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c10759 · Cited by 72

PROTAC 2.0: Expanding the frontiers of targeted protein degradation

Cornu, M., Lemaitre, T., Kieffer, C., & Voisin‐Chiret, A. S. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104376 · Cited by 71

Multimodal targeting chimeras enable integrated immunotherapy leveraging tumor-immune microenvironment

Lin, F., Yin, S., Zhang, Z., Yu, Y., Fang, H., Liang, Z., Zhu, R., Zhou, H., Li, J., Cao, K., et al. (2024) · Cell · doi:10.1016/j.cell.2024.10.016 · Cited by 72

CD36-mediated endocytosis of proteolysis-targeting chimeras

Wang, Z., Pan, B., Manne, R., Chen, J., Lv, D., Wang, M., Tran, P., Weldemichael, T., Yan, W., Zhou, H., et al. (2025) · Cell · doi:10.1016/j.cell.2025.03.036 · Cited by 71

Applications of covalent chemistry in targeted protein degradation

Lu, D., Yu, X., Lin, H., Cheng, R., Monroy, E. Y., Qi, X., Wang, M. C., & Wang, J. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00362g · Cited by 69

Targeted protein degradation in cancers: Orthodox PROTACs and beyond

Li, J., Chen, X., Lü, A., & Liang, C. (2023) · The Innovation · doi:10.1016/j.xinn.2023.100413 · Cited by 68

Insulin‐like Growth Factor 2‐Tagged Aptamer Chimeras (ITACs) Modular Assembly for Targeted and Efficient Degradation of Two Membrane Proteins

Tian, Y., Miao, Y., Guo, P., Wang, J., & Han, D. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202316089 · Cited by 64

Discovery of Exceptionally Potent, Selective, and Efficacious PROTAC Degraders of CBP and p300 Proteins

Thomas, J. E., Wang, M., Jiang, W., Wang, M., Wang, L., Wen, B., Sun, D., & Wang, S. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00492 · Cited by 60

Journey of PROTAC: From Bench to Clinical Trial and Beyond

Berkley, K., Zalejski, J., Sharma, N., & Sharma, A. K. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00577 · Cited by 62

Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment

Wu, H., Yao, H., He, C., Jia, Y., Zhu, Z., Xu, S., Li, D., & Xu, J. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.03.019 · Cited by 63

Applications and prospects of cryo-EM in drug discovery

Zhu, K., Yuan, C., Du, Y., Sun, K., Zhang, X., Vogel, H., Jia, X., Gao, Y., Zhang, Q., Wang, D., et al. (2023) · Military Medical Research · doi:10.1186/s40779-023-00446-y · Cited by 57

Novel approaches to targeted protein degradation technologies in drug discovery

Xue, Y., Bolinger, A. A., & Zhou, J. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2187777 · Cited by 59

Optimization of PROTAC Ternary Complex Using DNA Encoded Library Approach

Chen, Q., Liu, C., Wang, W., Meng, X., Cheng, X., Li, X.-Y., Cai, L., Luo, L., He, X., Qu, H., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.2c00797 · Cited by 55

DNA framework-engineered chimeras platform enables selectively targeted protein degradation

Zhou, L.-M., Yu, B., Gao, M., Chen, R., Li, Z., Gu, Y., Bian, J., & Ma, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-40244-7 · Cited by 61

Proteolysis-targeting drug delivery system (ProDDS): integrating targeted protein degradation concepts into formulation design

Chen, Y., Liu, F., Pal, S., & Hu, Q. (2024) · Chemical Society Reviews · doi:10.1039/d4cs00411f · Cited by 59

Enriching Proteolysis Targeting Chimeras with a Second Modality: When Two Are Better Than One

Salerno, A., Seghetti, F., Caciolla, J., Uliassi, E., Testi, E., Guardigni, M., Roberti, M., Milelli, A., & Bolognesi, M. L. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00302 · Cited by 58

Molecular glues and induced proximity: An evolution of tools and discovery

Robinson, S. A., Co, J., & Banik, S. M. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.04.001 · Cited by 58

Decoding the messaging of the ubiquitin system using chemical and protein probes

Henneberg, L. T., & Schulman, B. A. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.03.009 · Cited by 53

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

Li, S., Zeng, T., Wu, Z., Huang, J., Cao, X., Liu, Y., Bai, S., Chen, Q., Li, C., Lü, C., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c16438 · Cited by 52

Modeling the Effect of Cooperativity in Ternary Complex Formation and Targeted Protein Degradation Mediated by Heterobifunctional Degraders

Park, D. J., Izaguirre, J. A., Coffey, R., & Xu, H. (2022) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.2c00037 · Cited by 54

Degraders upgraded: the rise of PROTACs in hematological malignancies

Casan, J. M. L., & Seymour, J. F. (2024) · Blood · doi:10.1182/blood.2023022993 · Cited by 53

Linker-free PROTACs efficiently induce the degradation of oncoproteins

Zhang, J., Chen, C., Chen, X., Liao, K., Li, F., Song, X., Liu, C., Su, M.-Y., Sun, H., Hou, T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60107-7 · Cited by 51

Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges

Ye, P., Chi, X., Cha, J., Luo, S., Yang, G., Yan, X., & Yang, W. (2021) · Cells · doi:10.3390/cells10123309 · Cited by 51

Biophysical and Computational Approaches to Study Ternary Complexes: A ‘Cooperative Relationship’ to Rationalize Targeted Protein Degradation

Ward, J. A., Perez‐Lopez, C., & Mayor‐Ruiz, C. (2023) · ChemBioChem · doi:10.1002/cbic.202300163 · Cited by 48

The cyclimids: Degron-inspired cereblon binders for targeted protein degradation

Ichikawa, S., Payne, N. C., Xu, W., Chang, C., Vallavoju, N., Frome, S., Flaxman, H. A., Mazitschek, R., & Woo, C. M. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.01.003 · Cited by 49

Engineered platelets as targeted protein degraders and application to breast cancer models

Chen, Y., Pal, S., Li, W., Liu, F., Yuan, S., & Hu, Q. (2024) · Nature Biotechnology · doi:10.1038/s41587-024-02494-8 · Cited by 49

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

Yan, J., Li, T., Miao, Z., Wang, P., Sheng, C., & Zhuang, C. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00728 · Cited by 46

Nanoparticle‐Mediated Targeted Protein Degradation: An Emerging Therapeutics Technology

Baker, A., Ho, A. P. T., Itzhaki, L. S., & Fruk, L. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202503958 · Cited by 44

Degraders in epigenetic therapy: PROTACs and beyond

Dai, X., Ji, S., Fu, M., Liu, G.-Z., Liu, H., Wang, S., Shen, L., Wang, N., Herdewijn, P. A., Zheng, Y., et al. (2024) · Theranostics · doi:10.7150/thno.92526 · Cited by 45

Benchmarking Methods for PROTAC Ternary Complex Structure Prediction

Rovers, E., & Schapira, M. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c00426 · Cited by 41

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

Setia, N., Almuqdadi, H. T. A., & Abid, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.116041 · Cited by 42

Unconventional PROTACs for Targeted Protein Degradation in Cancer Therapy

Zhang, X., Song, Z., Zhang, X., Zou, J., Yu, G., Chen, X. S., & Wang, S. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202507702 · Cited by 43

Recent advances in targeted protein degraders as potential therapeutic agents

Yang, N., Kong, B., Zhu, Z., Huang, F., Zhang, L., Lu, T., Chen, Y., Zhang, Y., & Jiang, Y. (2023) · Molecular Diversity · doi:10.1007/s11030-023-10606-w · Cited by 44

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

Bond, A. G., Ordoño, M. M. I., Bisbach, C. M., Craigon, C., Makukhin, N., Caine, E. A., Nagala, M., Urh, M., Winter, G. E., Riching, K. M., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c11556 · Cited by 40

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

Fan, G., Chen, S., Zhang, Q., Yu, N., Shen, Z., Liu, Z., Guo, W., Tang, Z., Yang, J., & Liu, M. (2025) · MedComm · doi:10.1002/mco2.70401 · Cited by 48

Targeting bromodomain-containing proteins: research advances of drug discovery

Pan, Z., Zhao, Y., Wang, X., Xie, X., Liu, M., Zhang, K., Wang, L., Bai, D., Foster, L. J., Shu, R., et al. (2023) · Molecular Biomedicine · doi:10.1186/s43556-023-00127-1 · Cited by 43

Targeted Protein Degradation (TPD) for Immunotherapy: Understanding Proteolysis Targeting Chimera-Driven Ubiquitin-Proteasome Interactions

Kamaraj, R., Ghosh, S., Das, S., Sen, S., Kumar, P. R., Majumdar, M., Dasgupta, R., Mukherjee, S., Das, S., Ghose, I., et al. (2024) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.4c00253 · Cited by 37

Targeted protein degradation: current molecular targets, localization, and strategies

Pliatsika, D., Blatter, C., & Riedl, R. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104178 · Cited by 40

A comprehensive review of BET-targeting PROTACs for cancer therapy

Zhou, X., Zhao, F., Xu, Y.-T., Guan, Y., Yu, T., Zhang, Y., Duan, Y., & Zhao, Y. (2022) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2022.117033 · Cited by 36

Key Considerations in Targeted Protein Degradation Drug Discovery and Development

Qin, L., Dai, H., & Wang, J. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.934337 · Cited by 35

Chemically induced degradation of epigenetic targets

Kabir, M., Yu, X., Kanıskan, H. Ü., & Jin, J. J. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00100h · Cited by 36

Mathematical Model for Covalent Proteolysis Targeting Chimeras: Thermodynamics and Kinetics Underlying Catalytic Efficiency

Chaudhry, C. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c02076 · Cited by 35

Discovery of the GSH responsive “Y-PROTACs” targeting ALK and CDK4/6 as a potential treatment for cancer

Wang, S., Luo, D., Pu, C., Ma, X., Zhang, H., Feng, Z., Deng, R., Yu, S., Liu, Y., Huang, Q., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.115082 · Cited by 31

Novel formats of antibody conjugates: recent advances in payload diversity, conjugation, and linker chemistry

Fujii, T., & Matsuda, Y. (2023) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2023.2276873 · Cited by 32

The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells

Wolf, G., Craigon, C., Teoh, S. T., Essletzbichler, P., Onstein, S., Cassidy, D. M., Uijttewaal, E. C. H., Dvorak, V., Cao, Y., Bensimon, A., et al. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2024.11.009 · Cited by 34

Multimodal supramolecular targeting chimeras enable spatiotemporally resolved protein degradation in vivo

Liu, J., Ma, T., Yao, R., Li, L., Zheng, Q., & Wang, M. (2026) · Cell · doi:10.1016/j.cell.2025.12.007 · Cited by 31

Progress of small molecules for targeted protein degradation: PROTACs and other technologies

Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31

Current strategies for improving limitations of proteolysis targeting chimeras

Pu, C., Wang, S., Liu, L., Feng, Z., Zhang, H., Gong, Q., Sun, Y., Guo, Y., & Li, R. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.107927 · Cited by 32

Intrinsic signaling pathways modulate targeted protein degradation

Yuki, M., Akizuki, Y., Honda, R., Takao, M., Tsuchimoto, A., Hashimoto, S., Iio, H., Kato, M., Kaiho-Soma, A., Saeki, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49519-z · Cited by 30

Rational Design of PROTAC Linkers Featuring Ferrocene as a Molecular Hinge to Enable Dynamic Conformational Changes

Salerno, A., Wieske, L. H. E., Diehl, C. J., & Ciulli, A. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c18354 · Cited by 33

Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2

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Design, Synthesis, and Evaluation of Trivalent PROTACs Having a Functionalization Site with Controlled Orientation

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TACkling Cancer by Targeting Selective Protein Degradation

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Novel Amphiphilic PROTAC with Enhanced Pharmacokinetic Properties for ALK Protein Degradation

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Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics

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

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Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases

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Structural Basis of Conformational Dynamics in the PROTAC‐Induced Protein Degradation

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A programmable targeted protein-degradation platform for versatile applications in mammalian cells and mice

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Recent advances in dual PROTACs degrader strategies for disease treatment

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Rational design of the linkers in targeting chimeras

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Innovative, combinatorial and high-throughput approaches to degrader synthesis

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Dual-ligand PROTACS mediate superior target protein degradation in vitro and therapeutic efficacy in vivo

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High‐Throughput Miniaturized Synthesis of PROTAC‐Like Molecules

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Selective Degradation of TEADs by a PROTAC Molecule Exhibited Robust Anticancer Efficacy In Vitro and In Vivo

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Targeted Protein Degradation in Cancer: PROTACs, New Targets, and Clinical Mechanisms

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Multivalent binding kinetics resolved by fluorescence proximity sensing

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Advancing small-molecule drug discovery by encoded dual-display technologies

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Trivalent PROTACs Enhance Protein Degradation Through Cooperativity and AvidityPreprint

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Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation

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Targeted Protein Degradation with Small Molecules: How PROTACs Work

Ciulli, A. (2019) · Molecules Medicinal Chemistry Symposium (MMCS) · doi:10.3390/proceedings2019022115 · Cited by 1

Techniques for Accelerating the Understanding of PROTAC-Based Ternary Complex

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

Bond, A. G., Ordoño, M. M. I., Bisbach, C. M., Craigon, C., Makukhin, N., Caine, E. A., Nagala, M., Urh, M., Winter, G. E., Riching, K. M., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c11556 · Cited by 40