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 · see citing works

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 · see citing works

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 · see citing works

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 · see citing works

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 2,106 · see citing works

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 · see citing works

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 · see citing works

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 · see citing works

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 1,419 · see citing works

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 · see citing works

Factors affecting therapeutic compliance: A review from the patient’s perspective

Li, S.-C. (2008) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s1458 · Cited by 1,266 · see citing works

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 · see citing works

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

Fischer, E. S., Böhm, K., Lydeard, J. R., Yang, H., Stadler, M. B., Cavadini, S., Nagel, J., Serluca, F., Acker, V., Lingaraju, G. M., et al. (2014) · Nature · doi:10.1038/nature13527 · Cited by 1,141 · see citing works

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

Lu, J., Qian, Y., Altieri, M., Dong, H., Wang, J., Raina, K., Hines, J., Winkler, J. D., Crew, A. P., Coleman, K., et al. (2015) · Chemistry & Biology · doi:10.1016/j.chembiol.2015.05.009 · Cited by 1,140 · see citing works

Proteolysis: from the lysosome to ubiquitin and the proteasome

Ciechanover, A. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1552 · Cited by 1,133 · see citing works

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 · see citing works

Applications of CRISPR technologies in research and beyond

Barrangou, R., & Doudna, J. A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3659 · Cited by 1,005 · see citing works

The logic of the 26S proteasome.

Collins, G. A., & Goldberg, A. L. (2017) · Cell · doi:10.1016/j.cell.2017.04.023 · Cited by 933 · see citing works

The delivery of therapeutic oligonucleotides

Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 863 · see citing works

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 · see citing works

Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling

Li, W., Bengtson, M. H., Ulbrich, A., Matsuda, A., Reddy, V. A., Orth, A. P., Chanda, S. K., Batalov, S., & Joazeiro, C. A. P. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001487 · Cited by 839 · see citing works

Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins

Yang, N. J., & Hinner, M. J. (2015) · Methods in Molecular Biology · doi:10.1007/978-1-4939-2272-7_3 · Cited by 826 · see citing works

The emerging complexity of protein ubiquitination

Komander, D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370937 · Cited by 821 · see citing works

Polar Molecular Surface as a Dominating Determinant for Oral Absorption and Brain Penetration of Drugs

Kelder, J., Grootenhuis, P. D. J., Bayada, D. M., Delbressine, L. P. C., & Ploemen, J.-P. H. T. M. (1999) · Pharmaceutical Research · doi:10.1023/a:1015040217741 · Cited by 819 · see citing works

Small‐Molecule PROTACS: New Approaches to Protein Degradation

Toure, M., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507978 · Cited by 674 · see citing works

Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics

Schneekloth, A. R., Pucheault, M., Tae, H. S., & Crews, C. M. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.114 · Cited by 635 · see citing works

Modular PROTAC design for the degradation of oncogenic BCR-ABL

Lai, A. C., Toure, M., Hellerschmied, D., Salami, J., Jaime‐Figueroa, S., Ko, E., Hines, J., & Crews, C. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201507634 · Cited by 618 · see citing works

Targeted protein degradation by PROTACs

Neklesa, T. K., Winkler, J. D., & Crews, C. M. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.027 · Cited by 599 · see citing works

Targeting the von Hippel-Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction

Buckley, D. L., Van Molle, I., Gareiss, P. C., Tae, H. S., Michel, J., Noblin, D. J., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja209924v · Cited by 569 · see citing works

Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets

Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3321 · Cited by 563 · see citing works

Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs

Chamberlain, P. P., Lopez-Girona, A., Miller, K., Carmel, G., Pagarigan, B., Chie-Leon, B., Rychak, E., Corral, L. G., Ren, Y. J., Wang, M., et al. (2014) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2874 · Cited by 531 · see citing works

Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

Kisselev, A. F., van der Linden, W. A., & Overkleeft, H. S. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.003 · Cited by 528 · see citing works

HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins

Buckley, D. L., Raina, K., Darricarrere, N., Hines, J., Gustafson, J. L., Smith, I. E., Miah, A. H., Harling, J. D., & Crews, C. M. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00442 · Cited by 488 · see citing works

A Comprehensive Mathematical Model for Three-Body Binding Equilibria

Douglass, E. F., Miller, C. J., Sparer, G., Shapiro, H., & Spiegel, D. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja311795d · Cited by 472 · see citing works

Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation

Sakamoto, K. M., Kim, K. B., Verma, R., Ransick, A., Stein, B., Crews, C. M., & Deshaies, R. J. (2003) · Molecular & Cellular Proteomics · doi:10.1074/mcp.t300009-mcp200 · Cited by 425 · see citing works

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

Galdeano, C., Gadd, M. S., Soares, P., Scaffidi, S., Molle, I. V., Birced, I., Hewitt, S. H., Dias, D. M. G., & Ciulli, A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5011258 · Cited by 424 · see citing works

Targeted Protein Degradation: from Chemical Biology to Drug Discovery

Cromm, P. M., & Crews, C. M. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.05.024 · Cited by 423 · see citing works

Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras

Lebraud, H., Wright, D. J., Johnson, C. N., & Heightman, T. D. (2016) · ACS Central Science · doi:10.1021/acscentsci.6b00280 · Cited by 413 · see citing works

Perilous journey: a tour of the ubiquitin–proteasome system

Kleiger, G., & Mayor, T. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.12.003 · Cited by 409 · see citing works

Global analysis of cellular protein translation by pulsed SILAC

Schwanhäusser, B., Gossen, M., Dittmar, G., & Selbach, M. (2009) · PROTEOMICS · doi:10.1002/pmic.200800275 · Cited by 356 · see citing works

The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation

Weissman, A. M., Shabek, N., & Ciechanover, A. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3173 · Cited by 318 · see citing works

Going further than Lipinski's rule in drug design

Walters, W. P. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.648612 · Cited by 313 · see citing works

Small‐Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α

Buckley, D. L., Gustafson, J. L., Van Molle, I., Roth, A. G., Tae, H. S., Gareiss, P. C., Jorgensen, W. L., Ciulli, A., & Crews, C. M. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201206231 · Cited by 302 · see citing works

Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands

Remillard, D., Buckley, D. L., Paulk, J., Brien, G. L., Sonnett, M., Seo, H., Dastjerdi, S., Wühr, M., Dhe‐Paganon, S., Armstrong, S. A., et al. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201611281 · Cited by 294 · see citing works

Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?

Cohen, P., & Tcherpakov, M. (2010) · Cell · doi:10.1016/j.cell.2010.11.016 · Cited by 271 · see citing works

In Vivo Knockdown of Pathogenic Proteins via Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs)

Ohoka, N., Okuhira, K., Ito, M., Nagai, K., Shibata, N., Hattori, T., Ujikawa, O., Shimokawa, K., Sano, O., Koyama, R., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768853 · Cited by 240 · see citing works

Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface

Molle, I. V., Thomann, A., Buckley, D. L., So, E. C., Lang, S., Crews, C. M., & Ciulli, A. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.08.015 · Cited by 198 · see citing works

Pharmaceutical Amorphous Nanoparticles

Jog, R., & Burgess, D. J. (2016) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2016.09.014 · Cited by 186 · see citing works

Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells

Saenz, D. T., Fiskus, W. C., Qian, Y., Manshouri, T., Rajapakshe, K., Raina, K., Coleman, K. G., Crew, A. P. A., Shen, A., Mill, C. P., et al. (2017) · Leukemia · doi:10.1038/leu.2016.393 · Cited by 184 · see citing works

Oral Selective Estrogen Receptor Downregulators (SERDs), a Breakthrough Endocrine Therapy for Breast Cancer

McDonnell, D. P., Wardell, S. E., & Norris, J. D. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00760 · Cited by 178 · see citing works

Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand

Demizu, Y., Shibata, N., Hattori, T., Ohoka, N., Motoi, H., Misawa, T., Shoda, T., Naito, M., & Kurihara, M. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.09.041 · Cited by 125 · see citing works

Localization to the Proteasome Is Sufficient for Degradation

Janse, D. M., Crosas, B., Finley, D. J., & Church, G. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402954200 · Cited by 121 · see citing works

Targeted protein knockdown using small molecule degraders

Raina, K., & Crews, C. M. (2017) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2017.05.016 · Cited by 111 · see citing works

Oligonucleotide Therapeutics: Chemistry, Delivery and Clinical Progress

Sharma, V. K., & Watts, J. K. (2015) · Future Medicinal Chemistry · doi:10.4155/fmc.15.144 · Cited by 109 · see citing works

Rad23 escapes degradation because it lacks a proteasome initiation region

Fishbain, S., Prakash, S., Herrig, A., Elsasser, S., & Matouschek, A. T. (2011) · Nature Communications · doi:10.1038/ncomms1194 · Cited by 101 · see citing works

GABAA Receptor Subtype-Selective Modulators. II. α5-Selective Inverse Agonists for Cognition Enhancement

Atack, J. R. (2011) · Current Topics in Medicinal Chemistry · doi:10.2174/156802611795371314 · Cited by 85 · see citing works

Ubiquitin‐like domains can target to the proteasome but proteolysis requires a disordered region

Yu, H., Kago, G., Yellman, C. M., & Matouschek, A. T. (2016) · The EMBO Journal · doi:10.15252/embj.201593147 · Cited by 72 · see citing works

The Lysine48‐Based Polyubiquitin Chain Proteasomal Signal: Not a Single Child Anymore

Kravtsova‐Ivantsiv, Y., Sommer, T., & Ciechanover, A. J. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201205656 · Cited by 68 · see citing works

The Receptor Concept: A Continuing Evolution

Limbird, L. E. (2004) · Molecular Interventions · doi:10.1124/mi.4.6.6 · Cited by 61 · see citing works

Redirecting the specificity of ubiquitination by modifying ubiquitin-conjugating enzymes.

Gosink, M. M., & Vierstra, R. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9117 · Cited by 53 · see citing works

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 · see citing works

Characterization of a New Class of Androgen Receptor Antagonists with Potential Therapeutic Application in Advanced Prostate Cancer

Li, H., Hassona, M. D. H., Lack, N. A., Axerio-Cilies, P., Leblanc, E., Tavassoli, P., Kanaan, N., Frewin, K., Singh, K., Adomat, H. H., et al. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0267 · Cited by 28 · see citing works

Evaluation of a Diffusion-Driven Mechanism for Substrate Ubiquitination by the SCF-Cdc34 Ubiquitin Ligase Complex

Petroski, M. D., Kleiger, G., & Deshaies, R. J. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.10.010 · Cited by 21 · see citing works

Emerging Methods in Chemoproteomics with Relevance to Drug Discovery

Nguyen, C., West, G. M., & Geoghegan, K. F. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6539-7_2 · Cited by 19 · see citing works

Regulation of Proteasomal Degradation by Modulating Proteasomal Initiation Regions

Takahashi, K., Matouschek, A., & Inobe, T. (2015) · ACS Chemical Biology · doi:10.1021/acschembio.5b00554 · Cited by 13 · see citing works

Trial of thalidomide in insomnia associated with the third trimester

NULSEN, R. O. (1961) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)33360-3 · Cited by 5 · see citing works

Targeted protein degradation: expanding the toolbox

Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works

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 818 · see citing works

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

Khan, S., Zhang, X., Lv, D., Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0668-z · Cited by 688 · see citing works

PROTACs: great opportunities for academia and industry

Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y.-G., Tong, Y., & Rao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0101-6 · Cited by 651 · see citing works

PROTACs: An Emerging Therapeutic Modality in Precision Medicine

Nalawansha, D. A., & Crews, C. M. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.020 · Cited by 514 · see citing works

Differential PROTAC substrate specificity dictated by orientation of recruited E3 ligase

Smith, B. E., Wang, S. L., Jaime-Figueroa, S., Harbin, A., Wang, J., Hamman, B. D., & Crews, C. M. (2019) · Nature Communications · doi:10.1038/s41467-018-08027-7 · Cited by 517 · see citing works

Put a ring on it: application of small aliphatic rings in medicinal chemistry

Bauer, M. R., Fruscia, P. D., Lucas, S. C. C., Michaelides, I. N., Nelson, J. E., Storer, R. I., & Whitehurst, B. C. (2021) · RSC Medicinal Chemistry · doi:10.1039/d0md00370k · Cited by 500 · see citing works

Synthetic lethality as an engine for cancer drug target discovery

Huang, A., Garraway, L. A., Ashworth, A., & Weber, B. L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0046-z · Cited by 470 · see citing works

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

Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422 · see citing works

Current strategies for the design of PROTAC linkers: a critical review

Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424 · see citing works

Targeting the C481S ibrutinib-resistance mutation in Bruton’s tyrosine kinase using PROTAC-mediated degradation

Buhimschi, A. D., Armstrong, H. A., Toure, M., Jaime-Figueroa, S., Chen, T. L., Lehman, A. M., Woyach, J. A., Johnson, A. J., Byrd, J. C., & Crews, C. M. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00391 · Cited by 394 · see citing works

SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate

Roy, M. J., Winkler, S., Hughes, S. J., Whitworth, C., Galant, M., Farnaby, W., Rumpel, K., & Ciulli, A. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00092 · Cited by 386 · see citing works

Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

Dong, G., Ding, Y., He, S., & Sheng, C. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00895 · Cited by 369 · see citing works

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

Donovan, K. A., Ferguson, F. M., Bushman, J. W., Eleuteri, N. A., Bhunia, D., Ryu, S., Tan, L., Shi, K., Yue, H., Liu, X., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.038 · Cited by 359 · see citing works

Acquired Resistance to BET-PROTACs (Proteolysis-Targeting Chimeras) Caused by Genomic Alterations in Core Components of E3 Ligase Complexes

Zhang, L., Riley-Gillis, B., Vijay, P., & Shen, Y. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1129 · Cited by 365 · see citing works

MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53

Hines, J., Lartigue, S., Dong, H., Qian, Y., & Crews, C. M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2918 · Cited by 348 · see citing works

Antibody–PROTAC Conjugates Enable HER2-Dependent Targeted Protein Degradation of BRD4

Maneiro, M., Forte, N., Shchepinova, M. M., Kounde, C. S., Chudasama, V., Baker, J. R., & Tate, E. W. (2020) · ACS Chemical Biology · doi:10.1021/acschembio.0c00285 · Cited by 350 · see citing works

Degradation of proteins by PROTACs and other strategies

Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335 · see citing works

Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments

Yip, H. Y. K., & Papa, A. (2021) · Cells · doi:10.3390/cells10030659 · Cited by 332 · see citing works

Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action

Riching, K. M., Mahan, S. D., Corona, C. R., McDougall, M. G., Vasta, J. D., Robers, M. B., Urh, M., & Daniels, D. L. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00692 · Cited by 307 · see citing works

Chemistries of bifunctional PROTAC degraders

Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313 · see citing works

Exploring Targeted Degradation Strategy for Oncogenic KRASG12C

Zeng, M., Xiong, Y., Safaee, N., Nowak, R. P., Donovan, K. A., Yuan, C. J., Nabet, B., Gero, T. W., Feru, F., Li, L., et al. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2019.12.006 · Cited by 275 · see citing works

Inhibitors of protein–protein interactions (PPIs): an analysis of scaffold choices and buried surface area

Xu, R., & Gestwicki, J. E. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.06.004 · Cited by 262 · see citing works

Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges

Zeng, S., Huang, W., Zheng, X., Cheng, L., Zhang, Z., Wang, J., & Shen, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112981 · Cited by 262 · see citing works

Structure‐Based Design of a Macrocyclic PROTAC

Testa, A., Hughes, S. J., Lucas, X., Wright, J. E., & Ciulli, A. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201914396 · Cited by 251 · see citing works

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

Pike, A., Williamson, B., Harlfinger, S., Martin, S. W., & McGinnity, D. F. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.07.013 · Cited by 247 · see citing works

Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands

Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., Xu, T., Wang, M., Yang, C., Chinnaswamy, K., Stuckey, J. A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01393 · Cited by 229 · see citing works

Optical Control of Small Molecule-Induced Protein Degradation

Naro, Y., Darrah, K. E., & Deiters, A. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b12718 · Cited by 226 · see citing works

Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application

Yuan, X., Bu, H., Zhou, J., Yang, C., & Zhang, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00249 · Cited by 224 · see citing works

Proteolysis‐targeting chimeras in drug development: A safety perspective

Moreau, K., Coen, M., Zhang, A. X., Pachl, F., Castaldi, M. P., Dahl, G., Boyd, H., Scott, C., & Newham, P. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15014 · Cited by 229 · see citing works

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2

Mares, A., Miah, A. H., Smith, I. E. D., Rackham, M., Thawani, A. R., Cryan, J., Haile, P. A., Votta, B. J., Beal, A. M., Capriotti, C., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-0868-6 · Cited by 232 · see citing works

Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic

Hu, Z., & Crews, C. M. (2022) · ChemBioChem · doi:10.1002/cbic.202100270 · Cited by 231 · see citing works

Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015–2019)

Sánchez-Martínez, C., Lallena, M. J., Sanfeliciano, S. G., & de Dios, A. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.126637 · Cited by 200 · see citing works

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 198 · see citing works

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 198 · see citing works

<i>In Silico</i> Modeling of PROTAC-Mediated Ternary Complexes: Validation and Application

Drummond, M. L., & Williams, C. I. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00872 · Cited by 199 · see citing works

New-generation advanced PROTACs as potential therapeutic agents in cancer therapy

Wang, C., Zhang, Y., Chen, W., Wu, Y., & Xing, D. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02024-9 · Cited by 192 · see citing works

BacPROTACs mediate targeted protein degradation in bacteria

Morreale, F. E., Kleine, S., Leodolter, J., Junker, S., Hoi, D. M., Ovchinnikov, S., Okun, A., Kley, J., Kurzbauer, R., Junk, L., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.009 · Cited by 196 · see citing works

Targeted protein degradation as a powerful research tool in basic biology and drug target discovery

Wu, T., Yoon, H., Xiong, Y., Dixon-Clarke, S. E., Nowak, R. P., & Fischer, E. S. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0438-0 · Cited by 182 · 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

PROTACs: A novel strategy for cancer therapy

Liu, J., Ma, J., Liu, Y., Xia, J., Li, Y., Wang, Z. P., & Wei, W. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.006 · Cited by 186 · see citing works

PROTACs to address the challenges facing small molecule inhibitors

Martín-Acosta, P., & Xiao, X. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112993 · Cited by 186 · see citing works

Overview of Recent Strategic Advances in Medicinal Chemistry

Wu, G., Zhao, T., Kang, D., Zhang, J., Song, Y., Namasivayam, V., Kongsted, J., Pannecouque, C. C., Clercq, E. D., Poongavanam, V., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00359 · Cited by 183 · see citing works

Harnessing the Power of Proteolysis for Targeted Protein Inactivation

Verma, R., Mohl, D., & Deshaies, R. J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.01.010 · Cited by 185 · see citing works

FKBP Ligands—Where We Are and Where to Go?

Kolos, J. M., Voll, A. M., Bauder, M., & Hausch, F. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01425 · Cited by 158 · see citing works

Emerging strategies to overcome resistance to third-generation EGFR inhibitors

Shi, K., Wang, G., Pei, J., Zhang, J., Wang, J., Ouyang, L., Wang, Y., & Li, W. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01311-6 · Cited by 174 · see citing works

bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA)

Lim, S., Khoo, R., Peh, K. M., Teo, J., Chang, S. C., Ng, S., Beilhartz, G. L., Melnyk, R. A., Johannes, C. W., Brown, C. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1920251117 · Cited by 170 · 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

PROTACs– a game-changing technology

Konstantinidou, M., Li, J., Zhang, B., Wang, Z., Shaabani, S., ter Brake, F., Essa, K., & Dömling, A. S. S. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1659242 · Cited by 167 · see citing works

Discovery of GDC-0077 (Inavolisib), a Highly Selective Inhibitor and Degrader of Mutant PI3Kα

Hanan, E. J., Braun, M., Heald, R. A., MacLeod, C., Chan, C. C. C., Clausen, S., Edgar, K. A., Eigenbrot, C. W., Elliott, R. L., Endres, N., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01422 · Cited by 166 · see citing works

Targeting Brd4 for cancer therapy: inhibitors and degraders

Duan, Y., Guan, Y., Qin, W., Zhai, X., Yu, B., & Liu, H. (2018) · MedChemComm · doi:10.1039/c8md00198g · Cited by 165 · see citing works

How We Think about Targeting RNA with Small Molecules

Costales, M. G., Childs‐Disney, J. L., Haniff, H. S., & Disney, M. D. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01927 · Cited by 164 · see citing works

Cellular Resistance Mechanisms to Targeted Protein Degradation Converge Toward Impairment of the Engaged Ubiquitin Transfer Pathway

Ottis, P., Palladino, C., Thienger, P., Britschgi, A., Heichinger, C., Berrera, M., Julien-Laferrière, A., Roudnicky, F., Kam‐Thong, T., Bischoff, J. R., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00525 · Cited by 153 · see citing works

Expanding the arsenal of E3 ubiquitin ligases for proximity-induced protein degradation

Kannt, A., & Đikić, I. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.04.007 · Cited by 149 · see citing works

Bardoxolone conjugation enables targeted protein degradation of BRD4

Tong, B., Luo, M., Xie, Y., Spradlin, J. N., Tallarico, J. A., McKenna, J. M., Schirle, M., Maimone, T. J., & Nomura, D. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-72491-9 · Cited by 149 · see citing works

Theoretical Studies on the Molecular Properties, Toxicity, and Biological Efficacy of 21 New Chemical Entities

Srivastava, R. (2021) · ACS Omega · doi:10.1021/acsomega.1c03736 · Cited by 147 · see citing works

Amide-to-Ester Substitution as a Strategy for Optimizing PROTAC Permeability and Cellular Activity

Klein, V. G., Bond, A. G., Craigon, C., Lokey, R. S., & Ciulli, A. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01496 · Cited by 152 · see citing works

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Han, X., Zhao, L., Xiang, W., Qin, C., Miao, B., McEachern, D., Wang, Y., Metwally, H., Wang, L., Matvekas, A., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00882 · Cited by 170 · see citing works

DT2216—a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas

He, Y., Koch, R., Budamagunta, V., Zhang, P., Zhang, X., Khan, S., Thummuri, D., Ortiz, Y. T., Zhang, X., Lv, D., et al. (2020) · Journal of Hematology &amp; Oncology · doi:10.1186/s13045-020-00928-9 · Cited by 139 · see citing works

Targeted Degradation of PD‐L1 and Activation of the STING Pathway by Carbon‐Dot‐Based PROTACs for Cancer Immunotherapy

Su, W., Tan, M., Wang, Z., Zhang, J., Huang, W., Song, H., Wang, X., Ran, H., Gao, Y., Nie, G., et al. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202218128 · Cited by 137 · see citing works

A caged E3 ligase ligand for PROTAC-mediated protein degradation with light

Kounde, C. S., Shchepinova, M. M., Saunders, C. N., Muelbaier, M., Rackham, M. D., Harling, J. D., & Tate, E. W. (2020) · Chemical Communications · doi:10.1039/d0cc00523a · Cited by 136 · see citing works

Pharmacological Targeting of IRE1 in Cancer

Raymundo, D. P., Doultsinos, D., Guillory, X., Carlesso, A., Eriksson, L. A., & Chevet, É. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.07.006 · Cited by 136 · see citing works

Targeting IRAK4 for Degradation with PROTACs

Nunes, J., McGonagle, G. A., Eden, J., Kiritharan, G., Touzet, M., Lewell, X., Emery, J., Eidam, H., Harling, J. D., & Anderson, N. A. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00219 · Cited by 134 · see citing works

Discovery of an AKT Degrader with Prolonged Inhibition of Downstream Signaling

You, I., Erickson, E. C., Donovan, K. A., Eleuteri, N. A., Fischer, E. S., Gray, N. S., & Toker, A. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.11.014 · Cited by 132 · see citing works

Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

Zhao, Q., Ren, C., Liu, L., Chen, J., Shao, Y., Sun, N., Sun, R., Kong, Y., Ding, X., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01264 · Cited by 134 · see citing works

Targeted protein degradation and the enzymology of degraders

Fisher, S. L., & Phillips, A. J. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.004 · Cited by 126 · see citing works

Overcoming Cancer Drug Resistance Utilizing PROTAC Technology

Burke, M. R., Smith, A. R., & Zheng, G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.872729 · Cited by 126 · see citing works

Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2

Liu, Z., Hu, X., Wang, Q., Wu, X., Zhang, Q., Wei, W., Su, X., He, H., Zhou, S., Hu, R., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c02234 · Cited by 125 · see citing works

Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies

He, Y., Khan, S., Huo, Z., Lv, D., Zhang, X., Liu, X., Yuan, Y., Hromas, R., Xu, M., Zheng, G., et al. (2020) · Journal of Hematology &amp; Oncology · doi:10.1186/s13045-020-00924-z · Cited by 126 · see citing works

Development of a novel PROTAC using the nucleic acid aptamer as a targeting ligand for tumor selective degradation of nucleolin

Zhang, L., Li, L., Wang, X., Liu, H., Zhang, Y., Xie, T., Zhang, H., Li, X., Peng, T., Sun, X. H., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.09.008 · Cited by 122 · see citing works

Recent Developments in the Biology and Medicinal Chemistry of CDK9 Inhibitors: An Update

Wu, T., Qin, Z., Tian, Y., Wang, J., Xu, C., Li, Z., & Bian, J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00744 · Cited by 119 · see citing works

Bivalent Ligands for Protein Degradation in Drug Discovery

Scheepstra, M., Hekking, K. F. W., Hijfte, L. V., & Folmer, R. H. A. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.01.006 · Cited by 120 · see citing works

Strategies for designing proteolysis targeting chimaeras (PROTACs)

He, S., Dong, G., Cheng, J., Wu, Y., & Sheng, C. (2022) · Medicinal Research Reviews · doi:10.1002/med.21877 · Cited by 118 · see citing works

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

Zhang, X., Thummuri, D., Liu, X., Hu, W., Zhang, P., Khan, S., Yuan, Y., Zhou, D., & Zheng, G. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112186 · Cited by 123 · see citing works

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 122 · see citing works

Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands

Wang, Z., He, N., Guo, Z., Niu, C., Song, T., Guo, Y., Cao, K., Wang, A., Zhu, J., Zhang, X., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00919 · Cited by 120 · see citing works

Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations

Young, R. J., & Leeson, P. D. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00180 · Cited by 112 · see citing works

PDZ Domains as Drug Targets

Christensen, N. R., Čalyševa, J., Fernandes, E. F. A., Lüchow, S., Clemmensen, L. S., Haugaard‐Kedström, L. M., & Strømgaard, K. (2019) · Advanced Therapeutics · doi:10.1002/adtp.201800143 · Cited by 108 · see citing works

Targeted protein degrader development for cancer: advances, challenges, and opportunities

Fang, Y., Wang, S., Han, S., Zhao, Y., Yu, C., Liu, H., & Li, N. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.03.003 · Cited by 110 · see citing works

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

Xie, S., Zhu, J., Li, J., Zhan, F., Yao, H., Xu, J., & Xu, S. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00736 · Cited by 109 · see citing works

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 108 · see citing works

PROTACs: Emerging Targeted Protein Degradation Approaches for Advanced Druggable Strategies

Sincere, N. I., Anand, K., Ashique, S., Yang, J., & You, C. (2023) · Molecules · doi:10.3390/molecules28104014 · Cited by 109 · see citing works

Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders

Shen, Y., Gao, G., Yu, X., Kim, H., Wang, L., Xie, L., Schwarz, M. C., Chen, X., Guccione, E., Liu, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01111 · Cited by 107 · see citing works

A nano-predator of pathological MDMX construct by clearable supramolecular gold(I)-thiol-peptide complexes achieves safe and potent anti-tumor activity

Yan, S., Yan, J., Liu, D., Li, X., Kang, Q., You, W., Zhang, J., Wang, L., Tian, Z., Lu, W., et al. (2021) · Theranostics · doi:10.7150/thno.59020 · Cited by 107 · see citing works

Design and synthesis of selective degraders of EGFRL858R/T790M mutant

Zhang, X., Xu, F., Tong, L., Zhang, T., Xie, H., Lu, X., Ren, X., & Ding, K. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112199 · Cited by 109 · see citing works

Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK)

Lu, Y., & Sun, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01248 · Cited by 104 · see citing works

Discovery of potent small molecule PROTACs targeting mutant EGFR

Zhao, H., Yang, X., Lei, H., Xi, X.-X., Lu, S., Zhang, J., Xin, M., & Zhang, S. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112781 · Cited by 105 · see citing works

Targeting EZH2 for cancer therapy: From current progress to novel strategies

Zeng, J., Zhang, J., Sun, Y. J., Wang, J., Ren, C., Banerjee, S., Ouyang, L., & Wang, Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114419 · Cited by 108 · see citing works

PROTAC-mediated crosstalk between E3 ligases

Steinebach, C., Kehm, H., Lindner, S., Vu, L. P., Köpff, S., Mármol, Á. L., Weiler, C., Wagner, K. G., Reichenzeller, M., Krönke, J., et al. (2019) · Chemical Communications · doi:10.1039/c8cc09541h · Cited by 101 · see citing works

Targeting estrogen receptor α for degradation with PROTACs: A promising approach to overcome endocrine resistance

Lin, X., Xiang, H., & Luo, G. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112689 · Cited by 100 · see citing works

Covalent Small Molecules as Enabling Platforms for Drug Discovery

Dalton, S. E., & Campos, S. (2019) · ChemBioChem · doi:10.1002/cbic.201900674 · Cited by 98 · see citing works

The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022

Pang, X., Xu, W., Liu, Y., Li, H., & Chen, L. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115491 · Cited by 98 · see citing works

Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality

Kostić, M., & Jones, L. H. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.02.006 · Cited by 96 · see citing works

Effects of MTX-23, a Novel PROTAC of Androgen Receptor Splice Variant-7 and Androgen Receptor, on CRPC Resistant to Second-Line Antiandrogen Therapy

Lee, G. T., Nagaya, N., Desantis, J., Madura, K., Sabaawy, H. E., Kim, W.-J., Vaz, R. J., Cruciani, G., & Kim, I. Y. (2020) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0417 · Cited by 96 · see citing works

Discovery of a Highly Potent and Selective Dual PROTAC Degrader of CDK12 and CDK13

Yang, J., Chang, Y., Tien, J. C.-Y., Wang, Z., Zhou, Y., Zhang, P., Huang, W., Vo, J. N., Apel, I. J., Wang, C., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00384 · Cited by 96 · see citing works

Revisiting signal transducer and activator of transcription 3 (STAT3) as an anticancer target and its inhibitor discovery: Where are we and where should we go?

Huang, Q., Zhong, Y., Dong, H., Zheng, Q., Shi, S., Zhu, K., Qu, X., Hu, W., Zhang, X., & Wang, Y. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111922 · Cited by 93 · see citing works

Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands

Zhao, H., Wang, H., Mao, Y.-Z., Zhang, H., Xin, M., Xi, X.-X., Lei, H., Mao, S., Li, D., & Zhang, S. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01827 · Cited by 94 · see citing works

Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC)

Cao, F., de Weerd, S., Chen, D., Zwinderman, M. R. H., van der Wouden, P. E., & Dekker, F. J. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112800 · Cited by 91 · 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

Degrader–Antibody Conjugates: Emerging New Modality

Hong, K. B., & An, H. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01791 · Cited by 90 · see citing works

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 · see citing works

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

Sincere, N. I., Anand, K., Ashique, S., Yang, J., & You, C. (2023) · Molecules · doi:10.3390/molecules28104014 · Cited by 109 · see citing works

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 · see citing works

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

Huang, X., Wu, F., Ye, J., Wang, L., Wang, X., Li, X., & He, G. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.01.010 · Cited by 58 · see citing works