The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Abstract
MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“WB138 increases the levels of both p53 and MDM2, which is consistent with the activity of previous reports on MDM2 inhibitors[28,32–36].”
From Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries (2021) · cites this paper as [32]
In the citing paper
“Nutlin-3a had the strongest activity, and its binding activity with MDM2 reached 90 nM.”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [20]
In the citing paper
“At 200 mg/kg, twice a day, 20 days after oral administration of Nutlin-3a, the tumor growth inhibition rate reached 90%, with no obvious side effects [20].”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [20]
In the citing paper
“Moreover, others have shown that inhibition of MDM2 binding to p53 or p73α appears to be more effective at promoting p53- and p73α-mediated apoptosis in cancer cells compared with normal cells.19,45”
From Combination therapy in a xenograft model of glioblastoma: Enhancement of the antitumor activity of temozolomide by an MDM2 antagonist (2017) · cites this paper as [45]
In the citing paper
“Nutlin-3a is a small molecule, which binds to the N-terminal hydrophobic pocket of Mdm2 and blocks protein-protein interactions (PPIs) between Mdm2 and p53 (10).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [10]
In the citing paper
“It has been reported that a consequence of Nutlin treatment is elevated Mdm2 protein levels, and this occurs in cells with or without p53 (6,8).”
From Pharmacologically increasing Mdm2 Inhibits DNA repair and cooperates with genotoxic agents to kill p53-inactivated ovarian cancer cells (2015) · cites this paper as [6]
In the citing paper
“Nutlin-3 is a small molecule inhibitor of Mdm2/p53 interaction that can induce apoptosis in cancer cells through activation of p53.”
From Pharmacologically increasing Mdm2 Inhibits DNA repair and cooperates with genotoxic agents to kill p53-inactivated ovarian cancer cells (2015) · cites this paper as [6]
In the citing paper
“Nonmalignant tissues tolerate inhibition of Mdm2, and no overt toxicity was observed in preclinical in vivo models.9,11”
From Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death (2013) · cites this paper as [9]
In the citing paper
“For example, small molecule antagonism of the Mdm2–p53 interaction promotes p53-dependent tumor regression in murine models [102,103].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [103]
In the citing paper
“Small-molecule PPI antagonists that disrupt the p53–MDM2 interaction have been identified, including nutlin 3a96 and MI-219 (Ref. 97).”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [96]
In the citing paper
“To utilize MDM2 for the PROTAC system, the discovery of nutlins, small molecules that bind MDM2 at the p53 interaction interface, was a crucial step [66].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [66]
Citations
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801
Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53
Oliner, J. D., Pietenpol, J. A., Thiagalingam, S., Gyuris, J., Kinzler, K. W., & Vogelstein, B. (1993) · Nature · doi:10.1038/362857a0 · Cited by 1,474
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982
Research works printed but not linked: 3
- D. Freedman, A. J. Levine, Cell. Mol. Life Sci.5, 96 (1999).
- R. Zhang, H. Wang, Methods Mol. Med.85, 205 (2003).
- L. T. Vassilevet al., Anticancer Drug Des.13, 359 (2001).
Cited by
Sorted by citations
Items 301–400 of 1,103
Singer, S., Socci, N. D., Ambrosini, G., Sambol, E. B., DeCarolis, P. L., Wu, Y. V., O’Connor, R., Maki, R. G., Viale, A. J., Sander, C., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0584 · Cited by 249
Mechanism of p53 stabilization by ATM after DNA damage
Cheng, Q., & Chen, J. (2010) · Cell Cycle · doi:10.4161/cc.9.3.10556 · Cited by 264
USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses
Zou, Q., Jin, J., Hu, H., Li, H. S., Romano, S., Xiao, Y., Nakaya, M., Zhou, X., Cheng, X., Yang, P., et al. (2014) · Nature Immunology · doi:10.1038/ni.2885 · Cited by 253
Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site
Chen, S., Wu, J., Liang, Y., Tang, Y., Song, H., Wu, L., Xing, Y., Yan, N., Li, Y., Wang, Z., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.11.013 · Cited by 250
p53-based Cancer TherapyPreprint
Lane, D. P., Cheok, C. F., & Laı́n, S. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001222 · Cited by 251
p53 Negatively Regulates Transcription of the Pyruvate Dehydrogenase Kinase Pdk2
Contractor, T., & Harris, C. R. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1215 · Cited by 259
Targeting Tumor Suppressor p53 for Cancer Therapy: Strategies, Challenges and Opportunities
Hong, B., van den Heuvel, A. P. J., Prabhu, V. V., Zhang, S., & El‐Deiry, W. S. (2014) · Current Drug Targets · doi:10.2174/1389450114666140106101412 · Cited by 251
The Role of MDM2 Amplification and Overexpression in Tumorigenesis
Oliner, J. D., Saiki, A. Y., & Caenepeel, S. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026336 · Cited by 246
Structural conservation of druggable hot spots in protein–protein interfaces
Kozakov, D., Hall, D. R., Chuang, G., Cencic, R., Brenke, R., Grove, L. E., Beglov, D., Pelletier, J., Whitty, A., & Vajda, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1101835108 · Cited by 245
Kojima, K., Konopleva, M. Y., McQueen, T. J., O'Brien, S. M., Plunkett, W. K., & Andreeff, M. (2006) · Blood · doi:10.1182/blood-2005-12-5148 · Cited by 250
Maniaci, C., Hughes, S. J., Testa, A., Chen, W., Lamont, D. J., Rocha, S., Alessi, D. R., Romeo, R., & Ciulli, A. (2017) · Nature Communications · doi:10.1038/s41467-017-00954-1 · Cited by 245
Modulation of Protein–Protein Interactions for the Development of Novel Therapeutics
Πέττα, Ι., Lievens, S., Libert, C., Tavernier, J. H., & Bosscher, K. D. (2015) · Molecular Therapy · doi:10.1038/mt.2015.214 · Cited by 248
Martino, M. T. D., Leone, E., Amodio, N., Foresta, U., Lionetti, M., Pitari, M. R., Cantafio, M. E. G., Gullà, A., Conforti, F. S., Morelli, E., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1708 · Cited by 244
Messaoudi, K., Clavreul, A., & Lagarce, F. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.02.011 · Cited by 238
Allen, M. A., Andrysík, Z., Dengler, V. L., Mellert, H. S., Guarnieri, A. L., Freeman, J. A., Sullivan, K. D., Galbraith, M. D., Luo, X., Kraus, W. L., et al. (2014) · eLife · doi:10.7554/elife.02200 · Cited by 241
Bulatov, E., & Ciulli, A. (2015) · Biochemical Journal · doi:10.1042/bj20141450 · Cited by 237
Small molecule induced reactivation of mutant p53 in cancer cells
Liu, X., Wilcken, R., Joerger, A. C., Chuckowree, I., Amin, J., Spencer, J., & Fersht, A. R. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt305 · Cited by 246
Phosphorylation of p53 on Key Serines Is Dispensable for Transcriptional Activation and Apoptosis
Thompson, T., Tovar, C., Yang, H. S., Carvajal, D. M., Vu, B. T., Xu, Q., Wahl, G. M., Heimbrook, D. C., & Vassilev, L. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410233200 · Cited by 232
Self-citationRole of p53 in breast cancer progression: An insight into p53 targeted therapy
Marvalim, C., Datta, A., & Lee, S. C. (2023) · Theranostics · doi:10.7150/thno.81847 · Cited by 259
Recognition and Accommodation at the Androgen Receptor Coactivator Binding Interface
Hur, E., Pfaff, S. J., Payne, E. S., Grøn, H., Buehrer, B. M., & Fletterick, R. J. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020274 · Cited by 234
The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma
Slack, A., Chen, Z., Tonelli, R., Pulè, M. A., Hunt, L., Pession, A., & Shohet, J. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405495102 · Cited by 239
Coll-Mulet, L., Iglesias‐Serret, D., Santidrián, A. F., Cosialls, A. M., de Frías, M., Castaño, E., Campàs, C., Barragán, M., de Sevilla, A. F., Domingo, A., et al. (2006) · Blood · doi:10.1182/blood-2005-08-3273 · Cited by 236
Self-citationDiastereomeric spirooxindoles as highly potent and efficacious MDM2 inhibitors
Zhao, Y., Liu, L., Sun, W., Lu, J., McEachern, D., Li, X., Yu, S., Bernard, D., Ochsenbein, P., Ferey, V., et al. (2013) · Journal of the American Chemical Society · doi:10.1021/ja3125417 · Cited by 234
van Vugt, M. A. T. M., Gardino, A. K., Linding, R., Ostheimer, G. J., Reinhardt, H. C., Ong, S.-E., Tan, C. S. H., Miao, H., Keezer, S. M., Li, J., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000287 · Cited by 236
Valcourt, J. R., Lemons, J. M. S., Haley, E. M., Kojima, M. L., Demuren, O. O., & Coller, H. A. (2012) · Cell Cycle · doi:10.4161/cc.19879 · Cited by 240
Targeting NEDD8-Activated Cullin-RING Ligases for the Treatment of Cancer
Soucy, T. A., Smith, P. G., & Rolfe, M. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0343 · Cited by 222
Day, C. L., Chen, L., Richardson, S. J., Harrison, P. J., Huang, D. C. S., & Hinds, M. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m411434200 · Cited by 227
Smalley, K. S. M., Contractor, R., Haass, N. K., Kulp, A. N., Atilla‐Gokcumen, G. E., Williams, D. S., Bregman, H. S., Flaherty, K. T., Soengas, M. S., Meggers, E., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1538 · Cited by 239
E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points
Bricelj, A., Steinebach, C., Kuchta, R. D., Gütschow, M., & Sosič, I. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.707317 · Cited by 232
Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization
Graves, B., Thompson, T., Xia, M., Janson, C., Lukacs, C., Deo, D., Di Lello, P., Fry, D., Garvie, C., Huang, K.-S., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203789109 · Cited by 230
Self-citationp53 as a target for the treatment of cancer
Duffy, M. J., Synnott, N. C., McGowan, P. M., Crown, J. P., O’Connor, D. P., & Gallagher, W. M. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.10.004 · Cited by 239
Liu, M., Li, C., Pazgier, M., Li, C., Mao, Y., Lv, Y., Gu, B., Wei, G., Yuan, W., Zhan, C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008930107 · Cited by 236
The Genomic Landscape of Breast Cancer as a Therapeutic Roadmap
Ellis, M. J., & Perou, C. M. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0462 · Cited by 231
Morelli, X., Bourgeas, R., & Roche, P. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.05.024 · Cited by 223
Marine, J.-C. W., Dyer, M. A., & Jochemsen, A. G. (2007) · Journal of Cell Science · doi:10.1242/jcs.03362 · Cited by 228
Aggresome Formation and Neurodegenerative Diseases: Therapeutic Implications
Chin, L., Olzmann, J. A., & Li, L. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708783330692 · Cited by 233
Proteolysis-Targeting Chimeras: Induced Protein Degradation as a Therapeutic Strategy
Ottis, P., & Crews, C. M. (2017) · ACS Chemical Biology · doi:10.1021/acschembio.6b01068 · Cited by 228
PROTACs: An Emerging Targeting Technique for Protein Degradation in Drug Discovery
Gu, S., Cui, D., Chen, X., Xiong, X., & Zhao, Y. (2018) · BioEssays · doi:10.1002/bies.201700247 · Cited by 231
Zhu, H., Gao, H., Ji, Y., Zhou, Q., Du, Z., Tian, L., Jiang, Y., Yao, K., & Zhou, Z. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01314-3 · Cited by 223
Chemical approaches to the discovery and development of cancer therapies
Neidle, S., & Thurston, D. E. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1587 · Cited by 224
Polypharmacology: The science of multi-targeting molecules
Kabir, A., & Muth, A. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2021.106055 · Cited by 245
The ubiquitin-mediated protein degradation pathway in cancer: therapeutic implications
Burger, A. M., & Seth, A. K. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.07.006 · Cited by 229
Reciprocal repression between P53 and TCTP
Amson, R. B., Pece, S., Lespagnol, A., Vyas, R., Mazzarol, G., Tosoni, D., Colaluca, I. N., Viale, G., Rodrigues-Ferreira, S., Wynendaele, J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2546 · Cited by 232
Ubiquitination and Degradation of Mutant p53
Lukashchuk, N., & Vousden, K. H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00050-07 · Cited by 223
Kumamoto, K., Spillare, E. A., Fujita, K., Horikawa, I., Yamashita, T., Appella, E., Nagashima, M., Takenoshita, S., Yokota, J., & Harris, C. C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2780 · Cited by 231
Targeted protein degradation for cancer therapy
Hinterndorfer, M., Spiteri, V. A., Ciulli, A., & Winter, G. E. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00817-8 · Cited by 263
Textor, S., Fiegler, N., Arnold, A., Porgador, A., Hofmann, T. G., & Cerwenka, A. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3211 · Cited by 221
Specific Small Molecule Inhibitors of Skp2-Mediated p27 Degradation
Wu, L. I., Grigoryan, A. V., Li, Y., Hao, B., Pagano, M., & Cardozo, T. J. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.09.015 · Cited by 223
Molecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220
“Discovery of Nutlin-3, a promising inhibitor of MDM2 binding [176] energized the search for clinically active drugs.”
Backgroundp53-family proteins and their regulators: hubs and spokes in tumor suppression
Collavin, L., Lunardi, A., & Sal, G. D. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.35 · Cited by 225
Killing cancer cells by flipping the Bcl-2/Bax switch
Cory, S., & Adams, J. M. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.012 · Cited by 217
Tumor suppression and normal aging in mice with constitutively high p53 activity
Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A., & Perry, M. E. (2006) · Genes & Development · doi:10.1101/gad.1378506 · Cited by 210
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
Retinoid signaling regulates breast cancer stem cell differentiation
Ginestier, C., Wicinski, J., Cervera, N., Monville, F., Finetti, P., Bertucci, F., Wicha, M. S., Birnbaum, D., & Charafe‐Jauffret, E. (2009) · Cell Cycle · doi:10.4161/cc.8.20.9761 · Cited by 222
Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX
Hu, B., Gilkes, D. M., & Chen, J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1140 · Cited by 215
Relevance of the p53–MDM2 axis to aging
Wu, D., & Prives, C. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.187 · Cited by 215
Narrative Review: Protein Degradation and Human Diseases: The Ubiquitin Connection
Reinstein, E., & Ciechanover, A. J. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-9-200611070-00010 · Cited by 216
Translational Repression of C. elegans p53 by GLD-1 Regulates DNA Damage-Induced Apoptosis
Schumacher, B., Hanazawa, M., Lee, M., Nayak, S., Volkmann, K., Hofmann, R., Hengartner, M. O., Schedl, T., & Gartner, A. (2005) · Cell · doi:10.1016/j.cell.2004.12.009 · Cited by 221
Functionalised staple linkages for modulating the cellular activity of stapled peptides
Lau, Y. H., de Andrade, P., Quah, S. T., Rossmann, M., Laraia, L., Sköld, N., Sum, T. J., Rowling, P. J. E., Joseph, T. L., Verma, C. S., et al. (2014) · Chemical Science · doi:10.1039/c4sc00045e · Cited by 218
Mechanical cell competition kills cells via induction of lethal p53 levels
Wagstaff, L., Goschorska, M., Kozyrska, K., Duclos, G., Kuciński, I., Chessel, A., Hampton-O’Neil, L. A., Bradshaw, C. R., Allen, G. E., Rawlins, E. L., et al. (2016) · Nature Communications · doi:10.1038/ncomms11373 · Cited by 217
MDM2 Promotes Cell Motility and Invasiveness by Regulating E-Cadherin Degradation
Yang, J.-Y., Zong, C. S., Xia, W., Wei, Y., Ali-Seyed, M., Li, Z., Broglio, K., Berry, D. A., & Hung, M.-C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00172-06 · Cited by 211
Peptides mediating interaction networks: new leads at last
Neduva, V., & Russell, R. B. (2006) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2006.08.002 · Cited by 213
Transient Pockets on Protein Surfaces Involved in Protein−Protein Interaction
Eyrisch, S., & Helms, V. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070095g · Cited by 212
Yan, J., Yao, Y., Yan, S., Gao, R., Lu, W., & He, W. (2020) · Nano Letters · doi:10.1021/acs.nanolett.0c01757 · Cited by 214
Aguilar, A., Lu, J., Liu, L., Du, D., Bernard, D., McEachern, D., Przybranowski, S., Li, X., Luo, R., Wen, B., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01665 · Cited by 211
Tumour suppression by p53: the importance of apoptosis and cellular senescence
Zuckerman, V., Wolyniec, K., Sionov, R. V., Haupt, S., & Haupt, Y. (2009) · The Journal of Pathology · doi:10.1002/path.2584 · Cited by 222
PepSite: prediction of peptide-binding sites from protein surfaces
Trabuco, L. G., Lise, S., Petsalaki, E., & Russell, R. B. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks398 · Cited by 211
E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis
Lizé, M., Pilarski, S. M., & Dobbelstein, M. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.188 · Cited by 213
Liposarcoma: Molecular Genetics and Therapeutics
Conyers, R. K., Young, S., & Thomas, D. M. (2010) · Sarcoma · doi:10.1155/2011/483154 · Cited by 219
Nucleophosmin and its complex network: a possible therapeutic target in hematological diseases
Colombo, E., Alcalay, M., & Pelicci, P. G. (2011) · Oncogene · doi:10.1038/onc.2010.646 · Cited by 223
Stapled Peptides with Improved Potency and Specificity That Activate p53
Brown, C. J., Quah, S. T., Jong, J., Goh, A. M., Chiam, P. C., Khoo, K. H., Choong, M. L., Lee, M. A., Yurlova, L., Zolghadr, K., et al. (2012) · ACS Chemical Biology · doi:10.1021/cb3005148 · Cited by 206
Identification of SCF Ubiquitin Ligase Substrates by Global Protein Stability Profiling
Yen, H.-C. S., & Elledge, S. J. (2008) · Science · doi:10.1126/science.1160462 · Cited by 208
Abundance of Intrinsic Disorder in Protein Associated with Cardiovascular Disease
Cheng, Y., LeGall, T., Oldfield, C. J., Dunker, A. K., & Uversky, V. N. (2006) · Biochemistry · doi:10.1021/bi060981d · Cited by 203
Prognostic impact and targeting of CRM1 in acute myeloid leukemia
Kojima, K., Kornblau, S. M., Ruvolo, V. R., Dilip, A., Duvvuri, S. R., Davis, R. E., Zhang, M., Wang, Z., Coombes, K. R., Zhang, N., et al. (2013) · Blood · doi:10.1182/blood-2012-08-447581 · Cited by 210
Transient Activation of p53 in G2 Phase Is Sufficient to Induce Senescence
Krenning, L., Feringa, F. M., Shaltiel, I. A., van den Berg, J., & Medema, R. H. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.007 · Cited by 193
Protein–protein interactions as targets for small molecule drug discovery
Fry, D. C. (2006) · Biopolymers · doi:10.1002/bip.20608 · Cited by 203
Inflammation and p53: A Tale of Two Stresses
Gudkov, A. V., Gurova, K. V., & Komarova, E. A. (2011) · Genes & Cancer · doi:10.1177/1947601911409747 · Cited by 211
Identification of small-molecule antagonists that inhibit an activator:coactivator interaction
Best, J. L., Amezcua, C. A., Mayr, B. M., Flechner, L., Murawsky, C. M., Emerson, B. M., Zor, T., Gardner, K. H., & Montminy, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406374101 · Cited by 206
E3 Ubiquitin Ligases as Cancer Targets and Biomarkers
Sun, Y. (2006) · Neoplasia · doi:10.1593/neo.06376 · Cited by 210
Emerging New Concepts of Degrader Technologies
Ding, Y., Fei, Y., & Lu, B. (2020) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2020.04.005 · Cited by 204
Molecular networks for the study of TCM Pharmacology
Zhao, J., Jiang, P., & Zhang, W. (2009) · Briefings in Bioinformatics · doi:10.1093/bib/bbp063 · Cited by 206
Targeting the p53–MDM2 interaction to treat cancer
Klein, C., & Vassilev, L. T. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602164 · Cited by 204
Self-citationHolzer, P., Masuya, K., Furet, P., Kallen, J., Valat-Stachyra, T., Ferretti, S., Berghausen, J., Bouisset-Leonard, M., Buschmann, N., Pissot-Soldermann, C., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00810 · Cited by 203
DNA damage tolerance: a double-edged sword guarding the genome.
Ghosal, G., & Chen, J. (2013) · PubMed · doi:10.3978/j.issn.2218-676x.2013.04.01 · Cited by 215
Transcription Factor Activities Enhance Markers of Drug Sensitivity in Cancer
García‐Alonso, L., Iorio, F., Matchan, A., Fonseca, N. A., Jaaks, P., Peat, G., Pignatelli, M., Falcone, F., Benes, C. H., Dunham, I., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1679 · Cited by 199
The Chemical Biology of Reversible Lysine Post-translational Modifications
Wang, Z. A., & Cole, P. A. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.002 · Cited by 216
Neat1 is a p53-inducible lincRNA essential for transformation suppressionPreprint
Mello, S. S., Sinow, C., Raj, N., Mazur, P. K., Bieging-Rolett, K. T., Brož, D. K., Conklin, J. F., Vogel, H. S., Wood, L. D., Sage, J., et al. (2017) · Genes & Development · doi:10.1101/gad.284661.116 · Cited by 209
Poyurovsky, M. V., Priest, C., Kentsis, A., Borden, K. L., Pan, Z., Pavletich, N., & Prives, C. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601465 · Cited by 203
Dysregulation of p53/Sp1 Control Leads to DNA Methyltransferase-1 Overexpression in Lung Cancer
Lin, R.-K., Wu, C.-Y., Chang, J.-W., Juan, L., Hsu, H., Chen, C., Lu, Y.-Y., Tang, Y.-A., Yang, Y., Yang, P., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4161 · Cited by 208
Activation of p53 by MDM2 Antagonists Can Protect Proliferating Cells from Mitotic Inhibitors
Carvajal, D. M., Tovar, C., Yang, H. S., Vu, B. T., Heimbrook, D. C., & Vassilev, L. T. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3576 · Cited by 202
Self-citationToledo, F., Krummel, K. A., Lee, C. J., Liu, C.-W., Rodewald, L.-W., Tang, M., & Wahl, G. M. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.014 · Cited by 199
Therapeutic targeting of tumor suppressor genes
Morris, L. G. T., & Chan, T. A.-T. (2014) · Cancer · doi:10.1002/cncr.29140 · Cited by 209
Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling
Dhar, D., Antonucci, L., Nakagawa, H., Kim, J. Y., Glitzner, E., Caruso, S., Shalapour, S., Yang, L., Valasek, M. A., Lee, S., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.003 · Cited by 207
Systematic Targeting of Protein–Protein Interactions
Modell, A. E., Blosser, S. L., & Arora, P. S. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.05.008 · Cited by 184
Targeting the ubiquitin–proteasome system for cancer therapy
Shen, M., Schmitt, S. M., Buac, D., & Dou, Q. P. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.815728 · Cited by 204
Identification and Characterization of the First Small Molecule Inhibitor of MDMX
Reed, D., Shen, Y., Shelat, A. A., Arnold, L. A., Ferreira, A. M., Zhu, F., Mills, N., Smithson, D. C., Regni, C. A., Bashford, D., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056747 · Cited by 198
Translating p53-based therapies for cancer into the clinic
Peuget, S., Zhou, X., & Selivanova, G. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-023-00658-3 · Cited by 208
McFarland, J. M., Paolella, B. R., Warren, A., Geiger-Schuller, K., Shibue, T., Rothberg, M., Kuksenko, O., Colgan, W. N., Jones, A., Chambers, E., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17440-w · Cited by 173
Olefin Metathesis Reactions with Fluorinated Substrates, Catalysts, and Solvents
Fustero, S., Simón‐Fuentes, A., Barrio, P., & Haufe, G. (2014) · Chemical Reviews · doi:10.1021/cr500182a · Cited by 194
Protein-protein interaction modulators: advances, successes and remaining challenges
Mabonga, L., & Kappo, A. P. (2019) · Biophysical Reviews · doi:10.1007/s12551-019-00570-x · Cited by 200
Metadata
- Authors
- Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N., & Liu, E. A.
- Affiliations
- Department of Discovery Oncology, Roche Research Center, Hoffmann–La Roche, Inc., Nutley, NJ 07110, USA.
- Corresponding author
- Vassilev, Lyubomir T.
- Venue
- Science
- Published
- 2004-02-06
- Volume
- 303
- Issue
- 5659
- Pages
- 844-848
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2097933346
- Cited by
- 4,661
- References
- 21
- Citations by year
- 2026: 119 · 2025: 166 · 2024: 169 · 2023: 203 · 2022: 204 · 2021: 199 · 2020: 226 · 2019: 212 · 2018: 216 · 2017: 209 · 2016: 258 · 2015: 248 · 2014: 296 · 2013: 273 · 2012: 265
- FWCI
- 83.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- MDM2, p53, small molecule antagonists, p53 stabilization, p53-MDM2 interaction, cancer therapy, cell cycle arrest, apoptosis, tumor xenografts, crystal structure
- MeSH terms
- Animals, Binding Sites, Cell Cycle, Cell Division, Cell Line, Cell Survival, Crystallization, Dose-Response Relationship, Drug, Humans, Imidazoles, Mice, Nude, Models, Molecular, Molecular Weight, Neoplasm Transplantation, Neoplasms, Experimental, Nuclear Proteins, Phosphorylation, Piperazines, Protein Conformation, Proto-Oncogene Proteins, Stereoisomerism, Transplantation, Heterologous, Gene Expression, Genes, p53, Tumor Suppressor Protein p53, Cyclins, Apoptosis, Crystallography, X-Ray, NIH 3T3 Cells, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Mice, Proto-Oncogene Proteins c-mdm2, Hydrophobic and Hydrophilic Interactions
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
