PROTAC Cell Permeability and Oral Bioavailability: A Journey Into Uncharted Territory

DrugBank 5.0: a major update to the DrugBank database for 2018

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Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates

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Proteolysis targeting chimeras (PROTACs) in ‘beyond rule-of-five’ chemical space: Recent progress and future challenges

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Beyond the Rule of 5: Lessons Learned from AbbVie’s Drugs and Compound Collection

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Optimising proteolysis-targeting chimeras (PROTACs) for oral drug delivery: a drug metabolism and pharmacokinetics perspective

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Unraveling the Role of Linker Design in Proteolysis Targeting Chimeras

Bemis, T. A., Clair, J. J. L., & Burkart, M. D. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00482 · Cited by 244 · see citing works

PROTAC-DB: an online database of PROTACs

Weng, G., Shen, C., Cao, D., Gao, J., Dong, X., He, Q., Yang, B., Li, D., Wu, J., & Hou, T. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa807 · Cited by 219 · see citing works

Solution Conformations Shed Light on PROTAC Cell Permeability

Atilaw, Y., Poongavanam, V., Svensson Nilsson, C., Nguyen, D., Giese, A., Meibom, D., Erdelyi, M., & Kihlberg, J. (2021) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00556 · Cited by 208 · see citing works

PROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding

Tinworth, C. P., Lithgow, H., Dittus, L., Bassi, Z. I., Hughes, S. E., Muelbaier, M., Dai, H., Smith, I. E. D., Kerr, W. J., Burley, G. A., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01094 · Cited by 195 · see citing works

Fundamental aspects of DMPK optimization of targeted protein degraders

Cantrill, C., Chaturvedi, P., Rynn, C., Schaffland, J. P., Walter, I., & Wittwer, M. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.03.012 · Cited by 169 · see citing works

Understanding the Metabolism of Proteolysis Targeting Chimeras (PROTACs): The Next Step toward Pharmaceutical Applications

Goracci, L., Desantis, J., Valeri, A., Castellani, B., Eleuteri, M., & Cruciani, G. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00793 · Cited by 160 · see citing works

Developing degraders: principles and perspectives on design and chemical space

Maple, H. J., Clayden, N., Baron, A., Stacey, C., & Felix, R. L. (2019) · MedChemComm · doi:10.1039/c9md00272c · Cited by 159 · see citing works

Understanding and Improving the Membrane Permeability of VH032-Based PROTACs

Klein, V. G., Townsend, C. E., Testa, A., Zengerle, M., Maniaci, C., Hughes, S. J., Chan, K.-H., Ciulli, A., & Lokey, R. S. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00265 · Cited by 153 · see citing works

Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs

Danelius, E., Poongavanam, V., Peintner, S., Wieske, L. H. E., Erdélyi, M., & Kihlberg, J. O. (2020) · Chemistry - A European Journal · doi:10.1002/chem.201905599 · Cited by 128 · see citing works

A chemical approach for global protein knockdown from mice to non-human primates

Sun, X., Wang, J., Yao, X., Zheng, W., Mao, Y., Lan, T., Wang, L., Sun, Y., Zhang, X., Zhao, Q., et al. (2019) · Cell Discovery · doi:10.1038/s41421-018-0079-1 · Cited by 118 · see citing works

Conformational Sampling of Macrocyclic Drugs in Different Environments: Can We Find the Relevant Conformations?

Poongavanam, V., Danelius, E., Peintner, S., Alcaraz, L., Caron, G., Cummings, M. D., Wlodek, S. T., Erdélyi, M., Hawkins, P. C. D., Ermondi, G., et al. (2018) · ACS Omega · doi:10.1021/acsomega.8b01379 · Cited by 92 · see citing works

Systematic Investigation of the Permeability of Androgen Receptor PROTACs

Scott, D. E., Rooney, T. P. C., Bayle, E. D., Mirza, T., Willems, H. M. G., Clarke, J. H., Andrews, S. P., & Skidmore, J. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00194 · Cited by 79 · see citing works

Predicting the Permeability of Macrocycles from Conformational Sampling – Limitations of Molecular Flexibility

Poongavanam, V., Atilaw, Y., Ye, S., Wieske, L. H. E., Erdélyi, M., Ermondi, G., Caron, G., & Kihlberg, J. O. (2020) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2020.10.052 · Cited by 52 · see citing works

Degraders early developability assessment: face-to-face with molecular properties

Ermondi, G., Vallaro, M., & Caron, G. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.06.015 · Cited by 40 · see citing works

Arvinas unveils PROTAC structures

Halford, B. (2021) · Chemical & Engineering News · doi:10.47287/cen-09914-scicon1 · Cited by 12 · see citing works

Arvinas unveils PROTAC structures

Halford, B. A. (2021) · C&EN Global Enterprise · doi:10.1021/cen-09914-scicon1 · Cited by 9 · see citing works

PROTAC targeted protein degraders: the past is prologue

Békés, M., Langley, D. R., & Crews, C. M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00371-6 · Cited by 3,395 · see citing works

The current state of the art and future trends in RAS-targeted cancer therapies

Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549 · see citing works

Linker-Dependent Folding Rationalizes PROTAC Cell Permeability

Poongavanam, V., Atilaw, Y., Siegel, S., Giese, A., Lehmann, L. E., Meibom, D., Erdélyi, M., & Kihlberg, J. O. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00877 · Cited by 148 · see citing works

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 · see citing works

Current advances and development strategies of orally bioavailable PROTACs

Zeng, S., Ye, Y., Xia, H., Min, J., Xu, J., Wang, Z., Pan, Y., Zhou, X., & Huang, W. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115793 · Cited by 89 · see citing works

Trends in Molecular Properties, Bioavailability, and Permeability across the Bayer Compound Collection: Miniperspective

O’ Donovan, D. H., De Fusco, C., Kuhnke, L., & Reichel, A. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01577 · Cited by 83 · see citing works

Structural and Physicochemical Features of Oral PROTACs

Schade, M., Scott, J. S., Hayhow, T. G., Pike, A., Terstiege, I., Ahlqvist, M. M., Johansson, J. R., Diène, C. R., Fallan, C., Balazs, A., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01017 · Cited by 80 · see citing works

Hydrophobic tag-based protein degradation: Development, opportunity and challenge

He, Q., Zhao, X., Wu, D., Jia, S., Liu, C., Cheng, Z., Huang, F., Chen, Y., Lu, T., & Lü, S. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115741 · Cited by 70 · see citing works

PROTACs: A novel strategy for cancer drug discovery and development

Han, X., & Sun, Y. (2023) · MedComm · doi:10.1002/mco2.290 · Cited by 67 · see citing works

Targeted Protein Degradation: Advances, Challenges, and Prospects for Computational Methods

Mostofian, B., Martin, H., Razavi, A. M., Patel, S., Allen, B. K., Sherman, W., & Izaguirre, J. A. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00603 · Cited by 68 · see citing works

Exploring the chemical space of orally bioavailable PROTACs

Apprato, G., Poongavanam, V., Jiménez, D. G., Atilaw, Y., Erdélyi, M., Ermondi, G., Caron, G., & Kihlberg, J. O. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103917 · Cited by 67 · see citing works

Non-small molecule PROTACs (NSM-PROTACs): Protein degradation kaleidoscope

Ma, S., Ji, J., Tong, Y., Zhu, Y., Dou, J., Zhang, X., Xu, S., Zhu, T., Xu, X., You, Q., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.02.022 · Cited by 57 · see citing works

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

Mi, D., Li, Y., Gu, H., Li, Y., & Chen, Y. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115444 · Cited by 57 · see citing works

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 52 · see citing works

Impact of Linker Composition on VHL PROTAC Cell Permeability

Abeje, Y. E., Wieske, L. H. E., Poongavanam, V., Maassen, S., Atilaw, Y., Cromm, P. M., Lehmann, L. E., Erdélyi, M., Meibom, D., & Kihlberg, J. O. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02492 · Cited by 48 · see citing works

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 50 · see citing works

Predictive Modeling of PROTAC Cell Permeability with Machine Learning

Poongavanam, V., Kölling, F., Giese, A., Göller, A. H., Lehmann, L. E., Meibom, D., & Kihlberg, J. O. (2023) · ACS Omega · doi:10.1021/acsomega.2c07717 · Cited by 45 · see citing works

Radioactive ADME Demonstrates ARV-110’s High Druggability Despite Low Oral Bioavailability

He, Y., Zheng, Y., Zhu, C., Peng, L., Yu, J., Tang, C., Chen, H., & Diao, X. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01104 · Cited by 43 · see citing works

PROTACs: Current Trends in Protein Degradation by Proteolysis-Targeting Chimeras

Madan, J., Ahuja, V. K., Dua, K., Samajdar, S., Ramchandra, M., & Giri, S. (2022) · BioDrugs · doi:10.1007/s40259-022-00551-9 · Cited by 36 · see citing works

Natural product-based PROteolysis TArgeting Chimeras (PROTACs)

Liu, M., Martyn, A. P., & Quinn, R. J. (2022) · Natural Product Reports · doi:10.1039/d2np00038e · Cited by 28 · see citing works

Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs

Zhang, D., Ma, B., Dragovich, P. S., Ma, L., Chen, S., Chen, E. C., Ye, X., Liu, J., Pizzano, J., Bortolon, E., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00505-y · Cited by 27 · see citing works

Peptide-based PROTACs: Current Challenges and Future Perspectives

Wang, H., Chen, M., Zhang, X., Xie, S., Qin, J., & Li, J. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230130121822 · Cited by 26 · see citing works

Early evaluation of opportunities in oral delivery of PROTACs to overcome their molecular challenges

Yang, W., Saboo, S., Zhou, L., Askin, S., & Bak, A. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103865 · Cited by 24 · see citing works

Controlled bioorthogonal activation of Bromodomain-containing protein 4 degrader by co-delivery of PROTAC and Pd-catalyst for tumor-specific therapy

Li, Z., Jiang, T., Xu, Y., Li, B., Wu, C., Li, Y., Huang, Y. P., Xie, X., Pan, W., & Yuan, P. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.08.032 · Cited by 22 · see citing works

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

Vicente, A. T. S., Moura, S. P. S. P., & Salvador, J. A. R. (2025) · Communications Chemistry · doi:10.1038/s42004-025-01598-9 · Cited by 23 · see citing works

Industry perspective on the nonclinical safety assessment of heterobifunctional degraders

Hemkens, M. D., Stamp, K., Loberg, L. I., Moreau, K., & Hart, T. K. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103643 · Cited by 22 · see citing works

Hearing loss drug discovery and medicinal chemistry: Current status, challenges, and opportunities

Cousins, R. P. C. (2022) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2022.05.001 · Cited by 21 · see citing works

Targeted protein modification as a paradigm shift in drug discovery

Amirian, R., Azadi Badrbani, M., Izadi, Z., Samadian, H., Bahrami, G., Sarvari, S., Abdolmaleki, S., Nabavi, S. M., Derakhshankhah, H., & Jaymand, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115765 · Cited by 18 · see citing works

Linker Methylation as a Strategy to Enhance PROTAC Oral Bioavailability: Insights from Molecular Properties and Conformational Analysis

Jiménez, D. G., Ermondi, G., Jandová, Z., Vallaro, M., Caron, G., & Arnhof, H. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01497 · Cited by 18 · see citing works

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

Tian, L., Qiang, T., Yang, X., Yue, G., Zhai, X., Kang, K., Du, C., Lu, Q., Gao, H., Zhang, D., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115979 · Cited by 19 · see citing works

Degron tagging for rapid protein degradation in mice

Hernández-Morán, B. A., Taylor, G. C. A., Lorente‐Macías, Á., & Wood, A. J. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050613 · Cited by 15 · see citing works

The Evolving Paradigm of Antibody–Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases

High, P. C., Guernsey-Biddle, C., Subramanian, S., Jacob, J., & Carmon, K. S. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16070890 · Cited by 15 · see citing works

Discovery of Covalent MLKL PROTAC Degraders via Optimization of a Theophylline Derivative Ligand for Treating Necroptosis

Li, S., Ma, L., Li, X., Jiang, Y., Luo, Z., Yin, F., Zhang, Y., Chen, Y., Wan, S., Zhou, H., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00949 · Cited by 14 · see citing works

Development of a Buchwald–Hartwig Amination for an Accelerated Library Synthesis of Cereblon Binders

Lejava, A., Miseo, G. A., Phan, T., Zhu, J., Powers, H. L., Li, J., Mortensen, D. S., Zapf, C. W., Khambatta, G., Buenviaje, J., et al. (2024) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.4c00462 · Cited by 12 · see citing works

Design, synthesis and bioactivity evaluation of self-assembled PROTACs based on multi-target kinase inhibitors

Si, R., Zhu, H., Wang, J., Zhang, Q., Li, Y., Pan, X., & Zhang, J. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106439 · Cited by 11 · see citing works

Data-Driven Design of PROTAC Linkers to Improve PROTAC Cell Membrane Permeability

Murakami, Y., Ishida, S., Cho, N., Yuki, H., Ohta, M., Honma, T., Demizu, Y., & Terayama, K. (2026) · JACS Au · doi:10.1021/jacsau.6c00033 · Cited by 8 · see citing works

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

Zhang, S.-H., Zeng, N., Xu, J., Liu, C., Xu, M., Sun, J., An, Y., Zhong, X., Miao, L.-T., Wang, S., et al. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117584 · Cited by 7 · see citing works

Preparation and Characterization of Asds Improves the Solubility and Dissolution Performance of a Protac Drug

Zhang, H., Wu, H., Wang, L., Gao, Y., Machín, L., Zhao, Y., Wang, Z., Gao, L., & Han, J. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.106837 · Cited by 6 · see citing works

Topical BET PROTACs for locally restricted protein degradation in the lung

Hemmerling, M., Liu, J., Piras, A., Pehrson, R., Hedström, U., Cassani, C., Ranieri, B., Kwapień, K., Ribbing, K., Forss, C., et al. (2025) · RSC Medicinal Chemistry · doi:10.1039/d5md00173k · Cited by 5 · see citing works

Antibody Drug Conjugates (ADCs): Shaping the Future of Precision Oncology

Sevilla-Carrillo, I., García-Tercero, E., Alonso‐Moreno, C., & Moya‐López, C. (2025) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/0118715206348204241128063329 · Cited by 5 · see citing works

A Novel Gain-of-Signal Assay to Detect Targeted Protein Degradation

Hoffman, M., Cheah, K. M., & Wittrup, K. D. (2024) · ACS Synthetic Biology · doi:10.1021/acssynbio.3c00447 · Cited by 5 · see citing works

Tactics and Strategies for the Synthesis of Cereblon Ligands

Villemure, E., Nilewski, C., Wang, Y., Zhou, Y., & Wong, A. R. (2024) · Synthesis · doi:10.1055/s-0043-1775385 · Cited by 5 · see citing works

Structure-Informed Design of High-Cooperativity PROTAC Targeting SARS-CoV-2 RdRp via Click Chemistry and Enhanced Sampling Simulations

Shehzadi, K., Ran, Y., Kalsoom, I., Dong, J., Gao, P., Irfan, M., Yu, M., Meng, Z., & Liang, J. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c02065 · Cited by 4 · see citing works

Targeted degradation of BRD4 by PROTACs: advances in cancer therapy

Hong, Y., Liu, X., Li, Y., Yu, M., Wang, C., Nie, C., & Xu, S. (2026) · Chemical Communications · doi:10.1039/d5cc05563f · Cited by 4 · see citing works

A Chemically Induced CRISPR/dCas13FCPF Platform for Precise and Programmable RNA Regulation

Hasselbeck, S., Wang, J., Bai, Z., Hüfner, T., Hummer, G., Grote, P., & Cheng, X. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01609 · Cited by 4 · see citing works

Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems

Yao, T., Zhou, Z., Wang, G., Zhu, Z.-Y., & Li, X.-N. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-026-01853-2 · Cited by 3 · see citing works

Off-target autophagy disruption associated with a novel liver toxicity in dogs for a highly basic heterobifunctional protein degrader

Kath, J., Kohnken, R., Brayman, T. G., Yang, J., Haag, K., Gong, J., Untucht, C., Imhof, C., Robinson, K., McClure, R. A., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1664889 · Cited by 2 · see citing works

The In Vivo Effect of Amorphous Drug Nanoprecipitates on the Intestinal Absorption of the PROTACs ARV-110 (Bavdeglutamide) and ARV-471 (Vepdegestrant)

Niessen, J., Koziolek, M., Indulkar, A. S., Borchardt, T. B., Sjöblom, M., Hedeland, M., Lennernäs, H., & Dahlgren, D. (2026) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.6c00207 · Cited by 3 · see citing works

Permeability enhancer incorporated oral nanosuspension of ARV-825 PROTAC for Glioblastoma treatment

Patel, H., Yadav, A., Dukhande, V. V., & Patel, K. R. (2025) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-025-00771-5 · Cited by 2 · see citing works

Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations

Peng, X., Guo, S., Zheng, S., Hossain, A., Zhang, C., Mottamal, M., Skripnikova, E., Ma, P., Martinez-Carter, K., Zhang, Q., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01205 · Cited by 1 · see citing works

Enhancing Permeability Prediction of Heterobifunctional Degraders Using Machine Learning and Metadynamics-Informed 3D Molecular Descriptors

Kim, B., Sheridan, R. P., Zhang, R., de Barros, E. P., Johnston, J. M., & Li, X. (2025) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c01600 · Cited by 1 · see citing works

Conformation-Dependent Complexation Interactions for a SMARCA2 PROTAC and Cyclodextrin

Laramy, M. N. O., Napolitano, J. G., Zhou, Y., Russell, D. J., Robinson, S., Khirich, G., & Gobbi, A. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c01600 · Cited by 1 · see citing works

Assays for Measuring the Cell Permeability of Proteolysis-Targeting Chimeras (PROTACs): Performance, Correlations, Applicability and Recommendations

Brenner, C., Cui, Y., Schmidt, D., Kirchmair, J., Tan, L., & Braun, N. (2026) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c01908 · Cited by 1 · see citing works

Discovery of a Highly Potent and Efficient BRD9 Degrader with Strong In Vivo Antitumor Activity

Tang, X., Huang, Y., zhang, C., Sun, Y. W., Hu, Q. P., Cheng, G., Hu, J., Chen, Z., Zhang, X., Zhuang, X., et al. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00491 · Cited by 1 · see citing works

Proteolysis‐Targeting Chimeras (PROTACs)

Shen, L. (2025) · doi:10.1002/9781394300150.ch1 · Cited by 1 · see citing works

Construction of PROTAC Library via Liquid-Phase Synthesis Enabled by a Hydrophobic Tag

Zhou, Y., He, W., Zhou, Z., Wu, M. H., Wu, Q., Tao, Z., Zheng, M., Zhang, S., & Xu, T. (2026) · Organic Letters · doi:10.1021/acs.orglett.6c00263

Targeting 3CLpro for broad-spectrum antiviral therapy: Structural insights, inhibitor development, and the future of PROTACs

Zhang, B., Zhang, B., Xiong, H., Zhou, J., Wang, M., Tian, B., & Nan, J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-36518-8.00023-0

Atomic degradation: chemical design strategies and immunotherapeutic mechanisms of radio-PROTACs

Varol, T. Ö., & Varol, M. (2026) · Annals of Nuclear Medicine · doi:10.1007/s12149-026-02254-5

Advancing Biochemical Molecule Registration, Representation and Search for New Drug Modalities

Pinto-Gil, K., Maria, L. D., Noisier, A. F. M., Leung, S., Garon, A., Frolov, A. I., Chankeshwara, S. V., Bood, M., Brive, L., Tomkinson, N. P., et al. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6c00587

Programmable nanomedicine via bioorthogonal molecular engineering

Im, S., Koo, S., & Kim, J. S. (2026) · Nano Convergence · doi:10.1186/s40580-026-00568-8 · Cited by 1 · see citing works

Induced proximity-based therapeutics for advanced prostate cancer

Ching, J. M., Chau, C. H., & Figg, W. D. (2026) · npj Drug Discovery. · doi:10.1038/s44386-026-00062-5

Biomimetic internalin B-engineered liposomes enable PROTAC delivery across endothelial barriers

Peters, J., Christe, L., Bandomir, N. C., Roth, P., Klos, F., Heitel, P., Frangakis, A. S., Gier, S., Vogel‐Kindgen, S., & Windbergs, M. (2026) · Disease and Therapeutics · doi:10.1016/j.dist.2026.100022

Effects of intestinal permeation enhancers on solubilization and epithelial transport of the proteolysis targeting chimera (PROTAC) ARV-471 in rats

Niessen, J., Koziolek, M., Borchardt, T. B., Indulkar, A. S., Ortiz, B. J., Sjöblom, M., Hedeland, M., Lennernäs, H., & Dahlgren, D. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115340

From discovery to clinic: Medicinal chemistry strategies for PROTAC linker optimization

Yang, H., Gu, M., Li, Z., You, Q., & Wang, L. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2026.119327

BindingDB Entry 50023496: Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations.

BindingDB (2026) · UC San Diego · doi:10.7270/q2hq44tf

BindingDB Entry 50021664: Hydrophobic tag-based protein degradation: Development, opportunity and challenge.

BindingDB (2025) · UC San Diego · doi:10.7270/q280579x

BindingDB Entry 50022907: Impact of Linker Composition on VHL PROTAC Cell Permeability.

BindingDB (2026) · UC San Diego · doi:10.7270/q29w0mcr

BindingDB Entry 50022094: Discovery of Covalent MLKL PROTAC Degraders via Optimization of a Theophylline Derivative Ligand for Treating Necroptosis.

BindingDB (2025) · UC San Diego · doi:10.7270/q2q52v90

BindingDB Entry 50021125: Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection.

BindingDB (2025) · UC San Diego · doi:10.7270/q2jd52cc

BindingDB Entry 50021843: Structural and Physicochemical Features of Oral PROTACs.

BindingDB (2025) · UC San Diego · doi:10.7270/q2w09bm9

BindingDB Entry 50015833: Linker-Dependent Folding Rationalizes PROTAC Cell Permeability.

BindingDB (2023) · UC San Diego · doi:10.7270/q2qz2fzg

BindingDB Entry 50020409: Current advances of small molecule E3 ligands for proteolysis-targeting chimeras design.

BindingDB (2024) · UC San Diego · doi:10.7270/q2pv6qt5

BindingDB Entry 50023406: Development of a Buchwald-Hartwig Amination for an Accelerated Library Synthesis of Cereblon Binders.

BindingDB (2026) · UC San Diego · doi:10.7270/q27p949s

Challenges and Opportunities for In Vivo PROTAC Delivery

Benowitz, A. B., Scott‐Stevens, P., & Harling, J. D. (2021) · Future Medicinal Chemistry · doi:10.4155/fmc-2021-0223 · Cited by 29 · see citing works

Exploring the chemical space of orally bioavailable PROTACs

Apprato, G., Poongavanam, V., Jiménez, D. G., Atilaw, Y., Erdélyi, M., Ermondi, G., Caron, G., & Kihlberg, J. O. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103917 · Cited by 67 · see citing works

Protac tissue distribution

Steyn, S. J., Niosi, M., Jordan, S., Healy, C., & Rago, B. (2025) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2025.101192

The complexity of intestinal permeability and its implications on oral drug absorption and bioavailablity

Dahan, A. (2017) · Pharmaceutical Regulatory Affairs Open Access

Potential ADME-related issues for PROTACs

Hoffman, M. (2024) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2023.100590