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Prime time for PROTACs

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Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

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

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Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules

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Chemistries of bifunctional PROTAC degraders

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Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression

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Exploring Targeted Degradation Strategy for Oncogenic KRASG12C

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Waste disposal—An attractive strategy for cancer therapy

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Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations

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Proteolysis‐targeting chimeras in drug development: A safety perspective

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

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PROTAC-DB: an online database of PROTACs

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Antibody Conjugation of a Chimeric BET Degrader Enables <i>in vivo</i> Activity

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Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6

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DCAF11 Supports Targeted Protein Degradation by Electrophilic Proteolysis-Targeting Chimeras

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Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer

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

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Development of the first small molecule histone deacetylase 6 (HDAC6) degraders

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Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras

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Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy

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Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

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Bridged Proteolysis Targeting Chimera (PROTAC) Enables Degradation of Undruggable Targets

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Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer

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Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 1: Exploration of Antibody Linker, Payload Loading, and Payload Molecular Properties

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

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

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

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A potent KRAS macromolecule degrader specifically targeting tumours with mutant KRAS

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Selective degradation of CDK6 by a palbociclib based PROTAC

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Functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders

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

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Integrative Modeling of PROTAC-Mediated Ternary Complexes

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Plasticity of the Cullin-RING Ligase Repertoire Shapes Sensitivity to Ligand-Induced Protein Degradation

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

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Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

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

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Development of Selective Histone Deacetylase 6 (HDAC6) Degraders Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

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Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression

Wang, K., Dai, X., Yu, A., Feng, C., Liu, K., & Huang, L. (2022) · Journal of Experimental &amp; Clinical Cancer Research · doi:10.1186/s13046-022-02483-2 · Cited by 115 · see citing works

Antibody-mediated delivery of chimeric protein degraders which target estrogen receptor alpha (ERα)

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From Inhibition to Degradation: Targeting the Antiapoptotic Protein Myeloid Cell Leukemia 1 (MCL1)

Papatzimas, J. W., Gorobets, E., Maity, R., Muniyat, M. I., MacCallum, J. L., Neri, P., Bahlis, N. J., & Derksen, D. J. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00455 · Cited by 103 · see citing works

Assessing the Cell Permeability of Bivalent Chemical Degraders Using the Chloroalkane Penetration Assay

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Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations

Zhou, C., Fan, Z., Zhou, Z., Li, Y., Cui, R., Liu, C., Zhou, G., Diao, X., Jiang, H., Zheng, M., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01774 · Cited by 94 · see citing works

Discovery of thalidomide-based PROTAC small molecules as the highly efficient SHP2 degraders

Yang, X., Wang, Z., Pei, Y., Song, N., Xu, L., Feng, B., Wang, H., Luo, X., Hu, X., Qiu, X., et al. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2021.113341 · Cited by 85 · see citing works

Development of selective small molecule MDM2 degraders based on nutlin

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A novel cereblon modulator for targeted protein degradation

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Discovery of a Novel BCL-X_L PROTAC Degrader with Enhanced BCL-2 Inhibition

Pal, P., Thummuri, D., Lv, D., Liu, X., Zhang, P., Hu, W., Poddar, S. K., Hua, N., Khan, S., Yuan, Y., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00517 · Cited by 60 · see citing works

A highly accurate metadynamics-based Dissociation Free Energy method to calculate protein–protein and protein–ligand binding potencies

Wang, J., Ishchenko, A., Zhang, W., Razavi, A., & Langley, D. (2022) · Scientific Reports · doi:10.1038/s41598-022-05875-8 · Cited by 55 · see citing works

A critical evaluation of the approaches to targeted protein degradation for drug discovery

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Discovery of novel small molecule induced selective degradation of the bromodomain and extra-terminal (BET) bromodomain protein BRD4 and BRD2 with cellular potencies

Jiang, F., Wei, Q., Li, H., Li, H., Cui, Y., Ma, Y., Chen, H., Cao, P., Lu, T., & Chen, Y. (2020) · Bioorganic &amp; Medicinal Chemistry · doi:10.1016/j.bmc.2019.115181 · Cited by 48 · see citing works

Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders

Hu, J., Wei, J., Yim, H., Wang, L., Xie, L., Jin, M. S., Kabir, M., Qin, L., Chen, X., Liu, J., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01609 · Cited by 43 · see citing works

Identification and characterization of cancer vulnerabilities via targeted protein degradation

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Evaluating the Advantages of Using 3D-Enriched Fragments for Targeting BET Bromodomains

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Overexpression of bromodomain factor 3 in Trypanosoma cruzi ( Tc BDF 3) affects differentiation of the parasite and protects it against bromodomain inhibitors

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Discovery of Tetrahydroquinoxalines as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the Second Bromodomain

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Structural insights into the recognition of mono- and di-acetylated histones by the ATAD2B bromodomainPreprint

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GNE-235: A Lead Compound Selective for the Second Bromodomain of PBRM1

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