Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484

Global quantification of mammalian gene expression control

Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566

Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation

Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609

Breaking the chains: structure and function of the deubiquitinases

Komander, D., Clague, M. J., & Urbé, S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2731 · Cited by 1,969

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

Small-molecule inhibitors of protein–protein interactions: progressing towards the dream

Arkin, M. R., & Wells, J. A. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1343 · Cited by 1,705

Induced protein degradation: an emerging drug discovery paradigm

Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486

THE UBIQUITIN SYSTEM FOR PROTEIN DEGRADATION

Hershko, A., & Ciechanover, A. J. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.003553 · Cited by 1,448

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

BindingDB Entry 50007001: Overview of Recent Strategic Advances in Medicinal Chemistry.

BindingDB (2021) · UC San Diego · doi:10.7270/q2br8wfx

BindingDB Entry 50019498: Design, synthesis, and biological evaluation of Wee1 kinase degraders.

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BindingDB Entry 50018797: A bibliometric analysis of PROTAC from 2001 to 2021.

BindingDB (2024) · UC San Diego · doi:10.7270/q28p64s7

BindingDB Entry 50019583: The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022.

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BindingDB Entry 50017491: Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα.

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BindingDB Entry 50016375: Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13.

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BindingDB Entry 50023058: Discovery of a Selective and Orally Bioavailable RET Degrader with Effectiveness in Various Mutations.

BindingDB (2026) · UC San Diego · doi:10.7270/q2v4112f

BindingDB Entry 50017151: Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts.

BindingDB (2023) · UC San Diego · doi:10.7270/q2bv7mpd

BindingDB Entry 50012045: Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update.

BindingDB (2022) · UC San Diego · doi:10.7270/q2fb56k3

BindingDB Entry 50014278: Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening.

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BindingDB Entry 50012120: Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders.

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BindingDB Entry 50019285: Selective degradation of cellular BRD3 and BRD4-L promoted by PROTAC molecules in six cancer cell lines.

BindingDB (2024) · UC San Diego · doi:10.7270/q2pc36qn

BindingDB Entry 50016515: Nucleic-Acid-Based Targeted Degradation in Drug Discovery.

BindingDB (2023) · UC San Diego · doi:10.7270/q2k35zpc

BindingDB Entry 50008063: Targeting IRAK4 for Degradation with PROTACs.

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BindingDB Entry 50021622: Design, Synthesis, and Biological Evaluation of Potent and Selective PROTAC Degraders of Oncogenic KRASG12D.

BindingDB (2025) · UC San Diego · doi:10.7270/q2ww7pb2

BindingDB Entry 50002775: Inducing protein-protein interactions with molecular glues.

BindingDB (2020) · UC San Diego · doi:10.7270/q21g0px4

BindingDB Entry 50012315: Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC).

BindingDB (2022) · UC San Diego · doi:10.7270/q2ff3x1w

BindingDB Entry 50017059: Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor.

BindingDB (2023) · UC San Diego · doi:10.7270/q2959nk1

BindingDB Entry 50011296: Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application.

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BindingDB Entry 50018542: Drug Hunting at the Nexus of Medicinal Chemistry and Chemical Biology and the Discovery of Novel Therapeutic Modalities.

BindingDB (2024) · UC San Diego · doi:10.7270/q2m049pd

BindingDB Entry 50020612: Recent Advances on Small-Molecule Bromodomain-Containing Histone Acetyltransferase Inhibitors.

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BindingDB Entry 50019179: Targeted Protein Degradation Induced by HEMTACs Based on HSP90.

BindingDB (2024) · UC San Diego · doi:10.7270/q2125z03

BindingDB Entry 50010484: Design, synthesis and biological evaluation of Proteolysis Targeting Chimeras (PROTACs) as a BTK degraders with improved pharmacokinetic properties.

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BindingDB Entry 50018350: Recent advances in epigenetic proteolysis targeting chimeras (Epi-PROTACs).

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BindingDB Entry 50007380: Free Ligand 1D NMR Conformational Signatures To Enhance Structure Based Drug Design of a Mcl-1 Inhibitor (AZD5991) and Other Synthetic Macrocycles.

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BindingDB (2024) · UC San Diego · doi:10.7270/q2z60tgk

BindingDB Entry 50019408: Small-Molecule Hydrophobic Tagging: A Promising Strategy of Druglike Technology for Targeted Protein Degradation.

BindingDB (2024) · UC San Diego · doi:10.7270/q24x5d4t

BindingDB Entry 50009433: Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015-2019).

BindingDB (2021) · UC San Diego · doi:10.7270/q23f4t3t

BindingDB Entry 50020717: A beginner's guide to current synthetic linker strategies towards VHL-recruiting PROTACs.

BindingDB (2024) · UC San Diego · doi:10.7270/q2vh5t9d

BindingDB Entry 50019557: Discovery of NAFLD-Improving Agents by Promoting the Degradation of Keap1.

BindingDB (2024) · UC San Diego · doi:10.7270/q2s186w8

Small molecule-mediated protein knockdown as a new approach to drug discovery

Tinworth, C. P., Lithgow, H., & Churcher, I. (2016) · MedChemComm · doi:10.1039/c6md00347h · Cited by 32

Fehérje lebontást kiváltó, célzott kiméra vegyületek (PROTACs). Új, ígéretes irányzat a gyógyszerkutatásban : Molecular chimeras targeting protein degradation (PROTACs). Novel, promising concept in the contemporary drug discovery

Dormán, G. (2021) · Nemzetközi Vegyészkonferencia

PROTACs: Emerging Targeted Protein Degradation Approaches for Advanced Druggable Strategies

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Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules

Forrest, I., Conway, L. P., Gathmann, C., Jadhav, A. M., Chiu, T.-Y., Chaheine, C. M., Estrada, M. A., Shrestha, A., Sarris, K., Reitsma, J. M., et al. (2025) · ACS Central Science · doi:10.1021/acscentsci.5c01594 · Cited by 12

Expanding the horizons of targeted protein degradation: A non-small molecule perspective

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