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Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries

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Identification of probe-quality degraders for Poly(ADP-ribose) polymerase-1 (PARP-1)

Zhang, Z., Chang, X., Zhang, C., Zeng, S., Liang, M., Ma, Z., Wang, Z., Huang, W., & Shen, Z. (2020) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2020.1804382 · Cited by 46 · see citing works

Small-molecule correctors and stabilizers to target p53

Fallatah, M. M. J., Law, F. V., Chow, W. A., & Kaiser, P. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.02.007 · Cited by 44 · see citing works

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 44 · see citing works

Targeted Degradation of the Oncogenic Phosphatase SHP2

Vemulapalli, V., Donovan, K. A., Seegar, T. C. M., Rogers, J. M., Bae, M., Lumpkin, R. J., Cao, R., Henke, M. T., Ray, S. S., Fischer, E. S., et al. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00377 · Cited by 43 · see citing works

PROTACs, molecular glues and bifunctionals from bench to bedside: Unlocking the clinical potential of catalytic drugs

Maneiro, M., Vita, E. D., Conole, D., Kounde, C. S., Zhang, Q., & Tate, E. W. (2021) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2021.01.002 · Cited by 38 · see citing works

Design and linkage optimization of ursane-thalidomide-based PROTACs and identification of their targeted-degradation properties to MDM2 protein

Qi, Z., Yang, G., Deng, T., Wang, J., Zhou, H., Popov, S. A., Shults, E. E., & Wang, C. (2021) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2021.104901 · Cited by 39 · see citing works

An MDM2 degrader for treatment of acute leukemias

Marcellino, B. K., Yang, X., Kanıskan, H. Ü., Brady, C., Chen, H., Chen, K., Qiu, X., Clementelli, C., Herschbein, L., Li, Z., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01735-6 · Cited by 36 · see citing works

E3 ubiquitin ligases in cancer stem cells: key regulators of cancer hallmarks and novel therapeutic opportunities

Zou, Q., Liu, M., Liu, K., Zhang, Y., North, B. J., & Wang, B. (2023) · Cellular Oncology · doi:10.1007/s13402-023-00777-x · Cited by 33 · see citing works

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 · see citing works

An overview of PROTACs targeting MDM2 as a novel approach for cancer therapy

Li, H., Cai, X., Yang, X., & Zhang, X. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116506 · Cited by 29 · see citing works

Therapeutic Strategies to Activate p53

Aguilar, A., & Wang, S. (2022) · Pharmaceuticals · doi:10.3390/ph16010024 · Cited by 27 · see citing works

Anticancer strategies by upregulating p53 through inhibition of its ubiquitination by MDM2

Anifowose, A., Agbowuro, A. A., Yang, X., & Wang, B. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02574-9 · Cited by 25 · 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

Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core

Bazanov, D. R., Pervushin, N. V., Savin, E. V., Tsymliakov, M. D., Maksutova, A. I., Savitskaya, V. Y., Sosonyuk, S. E., Gracheva, Y. A., Seliverstov, M. Y., Lozinskaya, N. A., et al. (2022) · Pharmaceuticals · doi:10.3390/ph15040444 · Cited by 20 · see citing works

Sulfonamide derivatives of cis-imidazolines as potent p53-MDM2/MDMX protein-protein interaction inhibitors

Bazanov, D. R., Pervushin, N. V., Savin, E. V., Tsymliakov, M. D., Maksutova, A. I., Sosonyuk, S. E., Kopeina, G. S., & Lozinskaya, N. A. (2021) · Medicinal Chemistry Research · doi:10.1007/s00044-021-02802-w · Cited by 18 · see citing works

Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

Li, Q., Zhou, L., Qin, S., Huang, Z., Li, B., Li, B., Yang, M., Nice, E. C., Zhu, H., & Huang, C. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115447 · Cited by 17 · see citing works

Methods for computer-assisted PROTAC design

Rovers, E., & Schapira, M. (2023) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2023.06.020 · Cited by 17 · see citing works

An update patent review of MDM2–p53 interaction inhibitors (2019–2023)

Twarda‐Clapa, A. (2024) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2024.2419836 · Cited by 17 · see citing works

Manifold role of ubiquitin in Helicobacter pylori infection and gastric cancer

Sokolova, O. V., & Naumann, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03816-8 · Cited by 17 · see citing works

Dlx3 Ubiquitination by Nuclear Mdm2 Is Essential for Dentinogenesis in Mice

Zheng, H., Fu, J., Chen, Z., Yang, G., & Yuan, G. (2022) · Journal of Dental Research · doi:10.1177/00220345221077202 · Cited by 16 · see citing works

Small-Molecule Approaches to Target Transcription Factors

Cui, H., Stilgenbauer, M., & Koehler, A. N. (2024) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062722-012209 · Cited by 16 · see citing works

PROteolysis‐Targeting Chimeras (PROTACs) in leukemia: overview and future perspectives

Vicente, A. T. S., & Salvador, J. A. R. (2024) · MedComm · doi:10.1002/mco2.575 · Cited by 14 · see citing works

MDM2-BCL-XL PROTACs enable degradation of BCL-XL and stabilization of p53

Chang, M., Gao, F., Chen, J., Gnawali, G. R., & Wang, W. (2022) · Acta Materia Medica · doi:10.15212/amm-2022-0022 · Cited by 14 · see citing works

Chimera induced protein degradation: PROTACs and beyond

Yin, L., & Hu, Q. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112494 · Cited by 14 · see citing works

Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors

Dai, M., Sridhar, R., Li, R., Tan, R., Yan, K., Fan, G., & Liu, M. (2022) · Technology in Cancer Research & Treatment · doi:10.1177/15330338221095950 · Cited by 13 · see citing works

PROTACs: Novel approach for cancer breakdown by breaking proteins

Memon, H., & Patel, B. M. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120577 · Cited by 11 · see citing works

Heterobifunctional Ligase Recruiters Enable pan-Degradation of Inhibitor of Apoptosis Proteins

Ng, Y. L. D., Bricelj, A., Jansen, J. A., Murgai, A., Peter, K., Donovan, K. A., Gütschow, M., Krönke, J., Steinebach, C., & Sosič, I. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01817 · Cited by 11 · see citing works

Targeting reversible post-translational modifications with PROTACs: a focus on enzymes modifying protein lysine and arginine residues

Pichlak, M., Sobierajski, T., Błażewska, K. M., & Gendaszewska‐Darmach, E. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2254012 · Cited by 10 · see citing works

Design of Murine Double Minute 2 Proteolysis Targeting Chimera Degraders with a Built-In Tumor-Targeting Ability

Wang, Z., Yue, S., Chen, X., Li, J., Zhu, P., Chen, H., Qiu, F., Xie, D., Liang, Y., Li, D., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c01228 · Cited by 11 · see citing works

p53: The Multifaceted Roles of Covalent Modifications in Cancer

Grigoreva, T. A., Romanova, A. A., Tribulovich, V. G., Pestov, N. B., Oganov, R. A., Kovaleva, D. K., Korneenko, T. V., & Barlev, N. A. (2024) · Pharmaceuticals · doi:10.3390/ph17121682 · Cited by 10 · see citing works

A double-edged sword of neo-substrate degradation in PROTACs

Song, Z., Duan, C., Wu, M., Wang, Z., Pan, Y., Zhang, C., Huang, W., & Zeng, S. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118253 · Cited by 9 · see citing works

Synthetic approaches to constructing proteolysis targeting chimeras (PROTACs)

Bakulina, O., Sapegin, A., Bunev, A. S., & Krasavin, M. (2022) · Mendeleev Communications · doi:10.1016/j.mencom.2022.07.001 · Cited by 8 · see citing works

PROTAC Degraders

Ciulli, A., & Hsia, O. (2022) · doi:10.1002/9781119774198.ch9 · Cited by 8 · see citing works

Mdm2 targeting via PROteolysis TArgeting Chimeras (PROTAC) is efficient in p53 wildtype, p53-mutated, and abemaciclib-resistant estrogen receptor-positive cell lines and superior to mdm2 inhibition

Goerg, A., Piendl, G., Albert, V., Ortmann, O., Wege, A. K., & Brockhoff, G. (2025) · BMC Cancer · doi:10.1186/s12885-025-14361-z · Cited by 7 · see citing works

Synthesis and Antineoplastic Activity of a Dimer, Spiroindolinone Pyrrolidinecarboxamide

Cui, J., Wang, Y., Li, X., Xiao, F., Ren, H., & Wu, M. Y. (2023) · Molecules · doi:10.3390/molecules28093912 · Cited by 7 · see citing works

From Degraders to Molecular Glues: New Ways of Breaking Down Disease‐Associated Proteins

Nagel, Y. A., Britschgi, A., & Ricci, A. (2021) · Wiley eBooks · doi:10.1002/9783527826872.ch2 · Cited by 6 · see citing works

Targeting MDM2 for the development of a new cancer therapy: progress and challenges

Aguilar, A., Thomas, J. E., & Wang, S. (2023) · Medicinal Chemistry Research · doi:10.1007/s00044-023-03102-1 · Cited by 6 · see citing works

Recent Developments in Medicinal Chemistry and Therapeutic Potential of Anti-Cancer PROTACs-Based Molecules

Khan, M. Z. I., Nazli, A., Pan, Y., & Chen, J. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220803112409 · Cited by 7 · see citing works

Characterization of a dual degrader of MDM2 and GSPT1

Tandon, I., Esguerra, P. N., Li, C., Sun, H., Yang, K., Zhang, Z., Peng, J., & Tang, W. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117793 · Cited by 5 · see citing works

The evolution of Nutlins as p53-MDM2 inhibitors

Bazanov, D. R., & Lozinskaya, N. A. (2025) · Medicinal Chemistry Research · doi:10.1007/s00044-025-03492-4 · Cited by 3 · see citing works

Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies

Wang, W., Alley, A., Sun, N., Tadesse, M., Wang, X., & Zhang, R. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1663766 · Cited by 3 · see citing works

Dual inhibitor of MDM2 and NFAT1 for experimental therapy of breast cancer: in vitro and in vivo anticancer activities and newly discovered effects on cancer metabolic pathways

Wang, W., Aguilar, M., Datta, S., Alley, A., Tadesse, M., Wang, X., Gao, X., & Zhang, R. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1531667 · Cited by 2 · see citing works

Multi-Step Synthesis of Chimeric Nutlin–DCA Compounds Targeting Dual Pathways for Treatment of Cancer

Illuminati, D., Foschi, R., Marchetti, P., Zanirato, V., Fantinati, A., Trapella, C., Voltan, R., & Cristofori, V. (2025) · Molecules · doi:10.3390/molecules30193908 · Cited by 1 · see citing works

Design, synthesis, and anti-tumor activity of cyclic peptide–lenalidomide conjugated small molecules

Li, T., Li, T., Zhang, X., Xu, H., Xie, Y., Yan, R., Wu, X., Jin, Y., & Wang, Z. (2024) · New Journal of Chemistry · doi:10.1039/d3nj05320b · Cited by 1 · see citing works

Novel Technologies in PROTAC Design

Jain, K., Reddy, S. C., Moode, S., Mehra, P., Tarannum, S., Patel, M., Jain, V. K., & Popli, H. (2024) · Springer eBooks · doi:10.1007/978-981-97-5077-1_5 · Cited by 1 · see citing works

New N-substituted 2,4,5-triarylimidazolines: synthesis and antitumor activity

Султанова, Р. М., Bazanov, D. R., Kuleshina, G. Z., Lozinskaya, N. A., Svirshchevskaya, E. V., & ZLOTSKII, S. S. (2024) · Russian Chemical Bulletin · doi:10.1007/s11172-024-4483-4 · Cited by 1 · see citing works

Proteolysis Targeting Chimera (PROTAC) Design

(2023) · Royal Society of Chemistry eBooks · doi:10.1039/bk9781839167669-00158

Design of Mdm2 Protac Degraders with a Built-In Tumor-Targeting AbilityPreprint

Wang, Z., Yue, S., Chen, X., Li, J., Zhu, P., Chen, H., Qiu, F., Xie, D., Liang, Y., Li, D., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4845142

PROTACS- targeted protein degradation as a path to precision cancer therapeutics

Gatley, H. R., Fisher, P. B., & Das, S. K. (2025) · Advances in cancer research · doi:10.1016/bs.acr.2025.08.001

Additional file 1 of Degradation of neurodegenerative disease-associated TDP-43 aggregates and oligomers via a proteolysis-targeting chimera

Tseng, Y.-L., Lu, P.-C., Lee, C.-C., He, R.-Y., Huang, Y.-A., Tseng, Y.-C., Cheng, T.-J. R., Huang, J. J.-T., & Fang, J.-M. (2024) · Figshare · doi:10.6084/m9.figshare.26584962

Harnessing Targeted Protein Degradation for Developing Brain Cancer Therapy

Muhammad, O., White, S., Dumo, C. J., Park, T. I., Choi, P. J., & Jose, J. (2026) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.6c00123

Navigating the p53‐MDM2 Landscape: Molecular Insights and Therapeutic Strategies

Mansour, M. A., Hassan, G. S., & Abouzid, K. A. M. (2026) · Archiv der Pharmazie · doi:10.1002/ardp.70264

In vivo fate-guided design of efficient delivery systems for PROTACs: From molecular rationales to clinical progress

Zhang, W., Li, S., Yao, Y., Mao, Y., Jiang, W., & Li, S. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.109664

Predicting Ternary Complex Stability through Binding Free-Energy Calculations in the Geometric Route

Tan, B., Ciulli, A., & Michel, J. (2026) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.6c01541

BindingDB Entry 50018545: Blocking Non-enzymatic Functions by PROTAC-Mediated Targeted Protein Degradation.

BindingDB (2024) · UC San Diego · doi:10.7270/q26t0rwh

BindingDB Entry 50018659: Developments of CRBN-based PROTACs as potential therapeutic agents.

BindingDB (2024) · UC San Diego · doi:10.7270/q27948wc

BindingDB Entry 50014421: Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries.

BindingDB (2022) · UC San Diego · doi:10.7270/q2rb78fp

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 50018114: Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation.

BindingDB (2024) · UC San Diego · doi:10.7270/q2833x64

BindingDB Entry 50022109: An overview of PROTACs targeting MDM2 as a novel approach for cancer therapy.

BindingDB (2025) · UC San Diego · doi:10.7270/q2wq08f2

The p53 Super-Hub Architecture: From Planar to Volumetric Network Pharmacology

Bazanov, D. R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219752

Abstract 4870: Targeted MDM2 degradation as a novel and efficacious cancer therapy

Yang, J., Li, Y., Aguilar, A., McEachern, D., Przybranowski, S. A., Fernández‐Salas, E., & Lü, J. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-4870 · Cited by 1 · see citing works

MDM2 Degradation as a Novel and Efficacious Cancer Therapy

Yang, J. (2019) · Deep Blue (University of Michigan)

Development of novel PROTAC Small-Molecule Degraders of MDM2 Protein and Peptidomimetic Inhibitors Targeting WDR5-MLL1 Protein-Protein Interaction

Li, Y. (2018) · Deep Blue (University of Michigan)

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

Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312 · see citing works

Elevated MDM2 boosts the apoptotic activity of p53-MDM2 binding inhibitors by facilitating MDMX degradation

Xia, M., Knezevic, D., Tovar, C., Huang, B., Heimbrook, D. C., & Vassilev, L. T. (2008) · Cell Cycle · doi:10.4161/cc.7.11.5929 · Cited by 75 · see citing works