Disulfiram and 6-Thioguanine synergistically inhibit the enzymatic activities of USP2 and USP21

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

Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes.

Reyes-Turcu, F. E., Ventii, K. H., & Wilkinson, K. D. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.082307.091526 · Cited by 1,396 · see citing works

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

Skrott, Z., Mistrik, M., Andersen, K. K., Friis, S., Majera, D., Gursky, J., Ozdian, T., Bartkova, J., Turi, Z., Moudry, P., et al. (2017) · Nature · doi:10.1038/nature25016 · Cited by 807 · see citing works

Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer

Karran, P., & Attard, N. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2292 · Cited by 477 · see citing works

Drugging the undruggables: exploring the ubiquitin system for drug development

Huang, X., & Dixit, V. M. (2016) · Cell Research · doi:10.1038/cr.2016.31 · Cited by 427 · see citing works

The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer

Graner, E., Tang, D., Rossi, S., Baron, A., Migita, T., Weinstein, L. J., Lechpammer, M., Huesken, D., Zimmermann, J., Signoretti, S., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00055-8 · Cited by 368 · see citing works

Deubiquitinase inhibition as a cancer therapeutic strategy

D’Arcy, P., Wang, X., & Linder, S. T. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.002 · Cited by 312 · see citing works

The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2

Stevenson, L. F., Sparks, A., Allende‐Vega, N., Xirodimas, D. P., Lane, D. P., & Saville, M. K. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601567 · Cited by 280 · see citing works

Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes

Lin, M.-H., Moses, D. C., Hsieh, C.-H., Cheng, S.-C., Chen, Y., Sun, C., & Chou, C. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.12.015 · Cited by 251 · see citing works

Copper Signaling Axis as a Target for Prostate Cancer Therapeutics

Safi, R., Nelson, E. R., Chitneni, S. K., Franz, K. J., George, D. J., Zalutsky, M. R., & McDonnell, D. P. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3527 · Cited by 202 · see citing works

Emerging roles of deubiquitinases in cancer‐associated pathways

Sacco, J. J., Coulson, J. M., Clague, M. J., & Urbé, S. (2010) · IUBMB Life · doi:10.1002/iub.300 · Cited by 194 · see citing works

Dissection of USPcatalytic domains reveals five common insertion points

Ye, Y., Scheel, H., Hofmann, K., & Komander, D. (2009) · Molecular BioSystems · doi:10.1039/b907669g · Cited by 189 · see citing works

Disulfiram treatment of alcoholism

Wright, C., & Moore, R. D. (1990) · The American Journal of Medicine · doi:10.1016/0002-9343(90)90534-k · Cited by 183 · see citing works

Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models

Davis, M. I., Pragani, R., Fox, J. T., Shen, M., Parmar, K., Gaudiano, E. F., Liu, L., Tanega, C., McGee, L. E., Hall, M. D., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.738567 · Cited by 161 · see citing works

Inhibition of Ubiquitin-Specific Proteases as a Novel Anticancer Therapeutic Strategy

Yuan, T., Yan, F., Ying, M., Cao, J., He, Q., Zhu, H., & Yang, B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01080 · Cited by 144 · see citing works

Deubiquitinases and the new therapeutic opportunities offered to cancer

Pfoh, R., Lacdao, I. K., & Saridakis, V. (2015) · Endocrine Related Cancer · doi:10.1530/erc-14-0516 · Cited by 140 · see citing works

ReDO_DB: the repurposing drugs in oncology database

Pantziarka, P., Verbaanderd, C., Sukhatme, V. V., Capistrano, R., Crispino, S., Gyawali, B., Rooman, I., Nuffel, A. M. T. V., Meheus, L., Sukhatme, V. P., et al. (2018) · ecancermedicalscience · doi:10.3332/ecancer.2018.886 · Cited by 137 · see citing works

Liposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cellsin vitroandin vivo

Liu, P., Wang, Z., Brown, S., Kannappan, V., Patricia, T. E., Jiang, W. G., Irache, J. M., Tang, J. Z., Britland, S. T., Armesilla, A. L., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2166 · Cited by 124 · see citing works

Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage

Paranjpe, A., Zhang, R., Ali‐Osman, F., Bobustuc, G. C., & Srivenugopal, K. S. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt366 · Cited by 118 · see citing works

Disulfiram';s Anticancer Activity: Evidence and Mechanisms

Jiao, Y., Hannafon, B. N., & Ding, W. (2016) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520615666160504095040 · Cited by 112 · see citing works

Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition

Zha, J., Chen, F., Dong, H., Shi, P., Yao, Y., Zhang, Y., Li, R., Wang, S., Li, P., Wang, W., et al. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-163 · Cited by 108 · see citing works

USP7-specific inhibitors target and modify the enzyme’s active site via distinct chemical mechanisms.

Pozhidaeva, A., Valles, G., Wang, F., Wu, J., Sterner, D. E., Nguyen, P., Weinstock, J., Kumar, K. G. S., Kanyo, J., Wright, D., et al. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.09.004 · Cited by 107 · see citing works

FOXM1 Deubiquitination by USP21 Regulates Cell Cycle Progression and Paclitaxel Sensitivity in Basal-like Breast Cancer

Arceci, A., Bonacci, T., Wang, X., Stewart, K. G., Damrauer, J. S., Hoadley, K. A., & Emanuele, M. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.054 · Cited by 101 · see citing works

Inhibition of USP2 eliminates cancer stem cells and enhances TNBC responsiveness to chemotherapy

He, J., Lee, H., Saha, S., Ruan, D., Guo, H., & Chan, C. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1512-6 · Cited by 84 · see citing works

Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes

Issaenko, O. A., & Amerik, A. Y. (2012) · Cell Cycle · doi:10.4161/cc.20174 · Cited by 81 · see citing works

The role of UBL domains in ubiquitin-specific proteases

Faesen, A. C., Luna‐Vargas, M. P. A., & Sixma, T. K. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120004 · Cited by 66 · see citing works

Overview — In vitro inhibition of aldehyde dehydrogenase by disulfiram and metabolites

Lipsky, J. J., Shen, M. L., & Naylor, S. (2001) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(00)00224-6 · Cited by 65 · see citing works

Structural Basis for Inactivation of Giardia lamblia Carbamate Kinase by Disulfiram

Galkin, A. G., Kulakova, L., Lim, K., Chen, C. Z., Zheng, W., Turko, I. V., & Herzberg, O. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.553123 · Cited by 59 · see citing works

6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2

Chuang, S.-J., Cheng, S., Tang, H.-C., Sun, C.-Y., & Chou, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-21476-w · Cited by 59 · see citing works

USP2 promotes cell migration and invasion in triple negative breast cancer cell lines

Qu, Q., Mao, Y., Xiao, G., Fei, X., Wang, J., Zhang, Y., Liu, J., Cheng, G., Chen, X., Wang, J., et al. (2015) · Tumor Biology · doi:10.1007/s13277-015-3207-7 · Cited by 53 · see citing works

Disulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation

Kim, J. Y., Lee, N., Kim, Y. J., Cho, Y., An, H., Oh, E., Cho, T.-M., Sung, D., & Seo, J. H. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.022 · Cited by 44 · see citing works

Disulfiram and BKM120 in Combination with Chemotherapy Impede Tumor Progression and Delay Tumor Recurrence in Tumor Initiating Cell-Rich TNBC

Wu, L., Meng, F., Dong, L., Block, C. J., Mitchell, A. V., Wu, J. H., Jang, H., Chen, W., Polin, L., Yang, Q., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-35619-6 · Cited by 43 · see citing works

Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans

Díaz‐Sánchez, Á. G., ́Álvarez-Parrilla, E., Martı́nez-Martı́nez, A., Aguirre-Reyes, L. G., Orozpe-Olvera, J., Ramos-Soto, M., Núñez-Gastélum, J. A., Alvarado‐Tenorio, B., & la Rosa, L. A. D. (2016) · Molecules · doi:10.3390/molecules21121628 · Cited by 43 · see citing works

Disulfiram/copper causes redox-related proteotoxicity and concomitant heat shock response in ovarian cancer cells that is augmented by auranofin-mediated thioredoxin inhibition

Papaioannou, M., Mylonas, I. G., Kast, R. E., & Brüning, A. (2013) · Oncoscience · doi:10.18632/oncoscience.5 · Cited by 41 · see citing works

The role of deubiquitinases in breast cancer

Xiao, Z., Zhang, P., & Ma, L. (2016) · Cancer and Metastasis Reviews · doi:10.1007/s10555-016-9640-2 · Cited by 41 · see citing works

Cell Death and Deubiquitinases: Perspectives in Cancer

Bhattacharya, S., & Ghosh, M. K. (2014) · BioMed Research International · doi:10.1155/2014/435197 · Cited by 38 · see citing works

SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression

Lin, C.-H., Wong, S. H. K., Kurzer, J. H., Schneidawind, C., Wei, M. C., Duque‐Afonso, J., Jeong, J., Feng, X., & Cleary, M. L. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.124 · Cited by 34 · see citing works

Oxidizing to death

Brüning, A., & Kast, R. E. (2014) · Cell Cycle · doi:10.4161/cc.28959 · Cited by 34 · see citing works

Ubiquitin specific protease 21 upregulation in breast cancer promotes cell tumorigenic capability and is associated with the NOD-like receptor signaling pathway

Peng, L., Hu, Y., Chen, D., Linghu, R., Wang, Y., Kou, X., Yang, J., & Jiao, S. (2016) · Oncology Letters · doi:10.3892/ol.2016.5263 · Cited by 33 · see citing works

Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics

Loi, C., Day, J. D., Jue, S. G., Bush, E. D., Costello, P., Dewey, L. V., & Vestal, R. E. (1989) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1989.61 · Cited by 32 · see citing works

Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy

Spano, D., & Catara, G. (2023) · Cells · doi:10.3390/cells13010029 · Cited by 85 · see citing works

Nucleoside-based anticancer drugs: Mechanism of action and drug resistance

Hrubá, L., Das, V., Hajdúch, M., & Džubák, P. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115741 · Cited by 63 · see citing works

Ubiquitin–proteasome system as a target for anticancer treatment—an update

Kim, Y. J., Lee, Y., Shin, H. Y., Hwang, S., Park, J., & Song, E. J. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01455-0 · Cited by 57 · see citing works

USP21 promotes self-renewal and tumorigenicity of mesenchymal glioblastoma stem cells by deubiquitinating and stabilizing FOXD1

Zhang, Q., Chen, Z., Tang, Q., Wang, Z., Lu, J., You, Y., & Wang, H. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05163-3 · Cited by 32 · see citing works

Insights Into the Properties, Biological Functions, and Regulation of USP21

An, T., Lu, Y., Xu, Y. L., & Hou, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.944089 · Cited by 30 · see citing works

Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21

Göricke, F., Vu, V., Smith, L., Scheib, U., Böhm, R., Akkılıç, N., Wohlfahrt, G., Weiske, J., Bömer, U., Brzezinka, K., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01933 · Cited by 27 · see citing works

Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects

Bakkar, M., Khalil, S. I., Bhayekar, K., Kushwaha, N. D., Samarbakhsh, A., Dorandish, S., Edwards, H. J., Dou, Q. P., Ge, Y., & Gavande, N. S. (2025) · Biomolecules · doi:10.3390/biom15020240 · Cited by 25 · see citing works

Role of the USP family in autophagy regulation and cancer progression

Liu, C., Yuan, Y., Zhan, Y., Zou, M., Wu, L., Zhang, C., Chen, B., Zeng, H., Yang, R., Hu, T., et al. (2025) · APOPTOSIS · doi:10.1007/s10495-025-02095-z · Cited by 19 · see citing works

USP21-mediated G3BP1 stabilization accelerates proliferation and metastasis of esophageal squamous cell carcinoma via activating Wnt/β-Catenin signaling

Guo, J., Zhao, Y., Sui, H., Liu, L., Liu, F., Yang, L., Gao, F., Wang, J., Zhu, Y., Li, L., et al. (2024) · Oncogenesis · doi:10.1038/s41389-024-00524-3 · Cited by 17 · see citing works

The emerging role of deubiquitylating enzyme USP21 as a potential therapeutic target in cancer

Shi, Z.-Y., Li, C., Chen, R.-Y., Shi, J.-J., Lu, J., Lu, J., Yang, G., & Chen, J. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107400 · Cited by 14 · see citing works

Targeting the deubiquitinase USP2 for malignant tumor therapy (Review)

Zhang, S., Guo, Y., Zhang, S., Wang, Z. W., Zhang, Y., & Zuo, S. (2023) · Oncology Reports · doi:10.3892/or.2023.8613 · Cited by 14 · see citing works

Utilizing machine learning to identify nifuroxazide as an inhibitor of ubiquitin-specific protease 21 in a drug repositioning strategy

Tak, J., Nguyễn, T. K., Lee, K., Kim, S. G., & Ahn, H. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116459 · Cited by 9 · see citing works

Ubiquitin-specific proteases (USPs) in leukemia: a systematic review

Zangooie, A., Tavoosi, S., Arabhosseini, M., Halimi, A., Zangooie, H., Baghsheikhi, A. H., Rahgozar, S., Ahmadvand, M., Jarrahi, A. M., & Salehi, Z. (2024) · BMC Cancer · doi:10.1186/s12885-024-12614-x · Cited by 10 · see citing works

Ubiquitin Specific Protease 2: Structure% Isoforms% Cellular Function% Related Diseases and Its Inhibitors

Luo, H., Ji, Y., Gao, X., Liu, X., Wu, Y., & Wu, Y. (2022) · ONCOLOGIE · doi:10.32604/oncologie.2022.021705 · Cited by 8 · see citing works

Disulfiram impairs USP21-mediated MOF-K257 deubiquitination to inhibit esophageal squamous cell carcinoma progression

Yang, L., Sui, H., Ding, Y., Zhu, Y., Song, X., Zhang, Y., Fan, G., Wang, J., Cui, X., Jiang, Y., et al. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217419 · Cited by 7 · see citing works

Discovery of Baicalein as a Novel Ubiquitin‐Specific Protease 21 Inhibitor for the Treatment of Hepatocellular Carcinoma

Jia, H., Zhao, Z., Su, C., Du, J., Yang, S., Song, J., Han, X., Yu, F. H. Z., Sun, Z., & Chu, P. (2025) · Phytotherapy Research · doi:10.1002/ptr.70022 · Cited by 7 · see citing works

Identification of potential inhibitors of Ubiquitin carboxyl-terminal hydrolase 21 from repurposed drugs: Implications in anticancer therapeutics

Shamsi, A., Altwaijry, N. A., Shahwan, M. J., Ashames, A., Yadav, D. K., Furkan, M., & Khan, R. H. (2024) · Chemical Physics Impact · doi:10.1016/j.chphi.2024.100792 · Cited by 6 · see citing works

Disulfiram inhibits coronaviral main protease by conjugating to its substrate entry site

Kuan, Y., Chu, H.-F., Hsu, P., Hsu, K.-C., Lin, T.-H., Huang, C., & Chen, W. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.133955 · Cited by 5 · see citing works

Purine-based anticancer drugs

Elgemeie, G. H., & Mohamed‐Ezzat, R. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821783-2.00005-4 · Cited by 3 · see citing works

Targeting USP21 to inhibit abdominal aortic aneurysm progression by suppressing the phenotypic transition of vascular smooth muscle cells

Zhang, H.-D., Yue, H.-W., Sun, Y., Sun, G.-Z., Yang, K.-H., Jiang, T.-X., Cui, S.-M., Liu, Y., Guo, Y.-Y., Zhang, W.-C., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102328 · Cited by 4 · see citing works

Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence

Benkő, B.-M., De Brito Parreirinha, N. S., Sebe, I., & Zelkó, R. (2026) · iScience · doi:10.1016/j.isci.2026.115441 · Cited by 2 · see citing works

Molecular hybridization assisted multi-technique approach for designing USP21 inhibitors to halt catalytic triad-mediated nucleophilic attack and suppress pancreatic ductal adenocarcinoma progression: A molecular dynamics study

Roy, A., Sharma, S., Paul, I., & Ray, S. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.109096 · Cited by 1 · see citing works

USP2 in cancer: a double-edged sword and therapeutic target

Hao, P., Wan, J., Guo, Z., Zhang, Z., Hu, G., Liu, Y., Lei, H., Wu, Y., & Luo, H. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189689

BindingDB Entry 50018828: Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.

BindingDB (2024) · UC San Diego · doi:10.7270/q2k078hk

Disulfiram, and Disulfiram Derivatives as Novel Potential Anticancer Drugs Targeting the Ubiquitin Proteasome System in Both Preclinical and Clinical Studies

Kona, F. R., Buac, D., & Burger, A. M. (2011) · Current Cancer Drug Targets · doi:10.2174/156800911794519798 · Cited by 59 · see citing works

6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2

Chuang, S.-J., Cheng, S., Tang, H.-C., Sun, C.-Y., & Chou, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-21476-w · Cited by 59 · see citing works

Disulfiram is a slow-binding partial noncompetitive inhibitor of 20S proteasome activity

Hasinoff, B. B., & Patel, D. (2017) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2017.09.003 · Cited by 12 · see citing works

Two clinical drugs deubiquitinase inhibitor auranofin and aldehyde dehydrogenase inhibitor disulfiram trigger synergistic anti-tumor effects in vitro and in vivo

Huang, H., Liao, Y., Liu, N., Hua, X., Cai, J., Yang, C., Long, H., Zhao, C., Chen, X., Lan, X., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6425 · Cited by 65 · see citing works

Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity

Viola-Rhenals, M., Patel, K., Laura, J.-S., Wu, G., Liu, J., & Dou, Q. P. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867324666171023161121 · Cited by 91 · see citing works