The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound
Abstract
The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of low-molecular-weight compounds in order to identify compounds that can restore wild-type function to mutant p53. We found one compound capable of inducing apoptosis in human tumor cells through restoration of the transcriptional transactivation function to mutant p53. This molecule, named PRIMA-1, restored sequence-specific DNA binding and the active conformation to mutant p53 proteins in vitro and in living cells. PRIMA-1 rescued both DNA contact and structural p53 mutants. In vivo studies in mice revealed an antitumor effect with no apparent toxicity. This molecule may serve as a lead compound for the development of anticancer drugs targeting mutant p53.
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
“The small molecule APR-246 (PRIMA-1Met) can reactive mutant p53 in tumor cells and trigger cell death by apoptosis.”
From Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246 (2018) · cites this paper as [6]
In the citing paper
“Given that previous studies reported that eprenetapopt induces apoptosis (5, 24), we tested the effect of eprenetapopt in a cell line model incapable of undergoing apoptosis to rule out the dependency on apoptotic machinery for eprenetapopt-induced cell death.”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [24]
In the citing paper
“our findings are contrary to reports concluding that eprenetapopt induces apoptosis through mut-p53 reactivation (5, 24) and instead supports eprenetapopt as a ferroptosis inducer (20).”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [24]
In the citing paper
“Importantly, PRIMA-1 and its structural analog PRIMA-1MET (APR-246) inhibited tumor growth in mouse models of GBM [124,129,130].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [124]
In the citing paper
“As shown in Figure 5A, RITA and PRIMA-1 increased the expression of the p53 targets p21 and PUMA, based on qPCR measurements at 24 after their addition to cell cultures, similar to previous reports for other p53 mutants [36, 37].”
From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [37]
Citations
Cites
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
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · cited 1×
“It is particularly noteworthy that PRIMA-1 can reactivate His-175 mutant p53, which has extensive structural defect”
Backgroundp53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,346
A Matter of Life and Cell Death
Evan, G. I., & Littlewood, T. D. (1998) · Science · doi:10.1126/science.281.5381.1317 · Cited by 1,528
p53 Status and the Efficacy of Cancer Therapy in Vivo
Lowe, S. W., Bodis, S. B., McClatchey, A. I., Remington, L., Ruley, H. E., Fisher, D. E., Housman, D. E., & Jacks, T. (1994) · Science · doi:10.1126/science.7973635 · Cited by 1,468
The complexity of p53 modulation: emerging patterns from divergent signalsPreprint
Giaccia, A. J., & Kastan, M. B. (1998) · Genes & Development · doi:10.1101/gad.12.19.2973 · Cited by 1,315
Disruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044
Regulation of the specific DNA binding function of p53
Hupp, T. R., Meek, D. W., Midgley, C., & Lane, D. P. (1992) · Cell · doi:10.1016/0092-8674(92)90562-q · Cited by 916
Pharmacological Rescue of Mutant p53 Conformation and Function
Foster, B. A., Coffey, H. A., Morin, M. J., & Rastinejad, F. (1999) · Science · doi:10.1126/science.286.5449.2507 · Cited by 802
Tumor surveillance via the ARF–p53 pathwayPreprint
Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.19.2984 · Cited by 718
Flagged first, then by citations
Cited by
Sorted by citations
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473
Vousden, K. H., & Lane, D. P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2147 · Cited by 2,351
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis
Chen, Z., Trotman, L. C., Shaffer, D., Lin, H.-K., Dotan, Z. A., Niki, M., Koutcher, J. A., Scher, H. I., Ludwig, T., Gerald, W., et al. (2005) · Nature · doi:10.1038/nature03918 · Cited by 1,993
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820
Mutant p53 in Cancer: New Functions and Therapeutic Opportunities
Muller, P. A. J., & Vousden, K. H. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.01.021 · Cited by 1,545
Mutant p53: one name, many proteinsPreprint
Freed-Pastor, W. A., & Prives, C. L. (2012) · Genes & Development · doi:10.1101/gad.190678.112 · Cited by 1,290
Venselaar, H., Beek, T. A. H. T., Kuipers, R. K. P., Hekkelman, M. L., & Vriend, G. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-548 · Cited by 1,201
Haupt, S., Berger, M., Goldberg, Z., & Haupt, Y. (2003) · Journal of Cell Science · doi:10.1242/jcs.00739 · Cited by 1,136
MicroRNAs in Development and Disease
Sayed, D. H., & Abdellatif, M. (2011) · Physiological Reviews · doi:10.1152/physrev.00006.2010 · Cited by 1,101
mCSM: Predicting the effects of mutations in proteins using graph-based signatures
Pires, D. E. V., Ascher, D. B., & Blundell, T. L. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt691 · Cited by 1,066
Targeting p53 pathways: mechanisms, structures, and advances in therapy
Wang, H., Guo, M., Wei, H., & Chen, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01347-1 · Cited by 1,016
Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889
Self-citationAwakening guardian angels: drugging the p53 pathway
Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2763 · Cited by 881
Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting
Borrero, L. J. H., & El‐Deiry, W. S. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188556 · Cited by 805
Mutant p53 Gain-of-Function in CancerPreprint
Oren, M., & Rotter, V. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001107 · Cited by 778
Role of p53 in Cell Death and Human Cancers
Ozaki, T., & Nakagawara, A. (2011) · Cancers · doi:10.3390/cancers3010994 · Cited by 650
Drugging p53 in cancer: one protein, many targets
Hassin, O., & Oren, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00571-8 · Cited by 771
Drugging the p53 pathway: understanding the route to clinical efficacy
Khoo, K. H., Verma, C. S., & Lane, D. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4236 · Cited by 742
Apoptosis: a basic biological phenomenon with wide‐ranging implications in human disease
Fadeel, B., & Orrenius, S. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2005.01570.x · Cited by 727
Urothelial tumorigenesis: a tale of divergent pathways
Wu, X. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1697 · Cited by 696
The role of ubiquitination in tumorigenesis and targeted drug discovery
Deng, L., Meng, T., Chen, L., Wei, W., & Wang, P. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0107-0 · Cited by 744
The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches
Joerger, A. C., & Fersht, A. R. (2016) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014710 · Cited by 675
Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623
Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth
Germano, G., Lamba, S., Rospo, G., Barault, L., Magrì, A., Maione, F., Russo, M., Crisafulli, G., Bartolini, A., Lerda, G., et al. (2017) · Nature · doi:10.1038/nature24673 · Cited by 638
The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance
Bouwman, P., & Jonkers, J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3342 · Cited by 615
PRIMA-1 reactivates mutant p53 by covalent binding to the core domain
Lambert, J. M. R., Gorzov, P., Veprintsev, D. B., Söderqvist, M., Segerbäck, D., Bergman, J., Fersht, A. R., Hainaut, P., Wiman, K. G., & Bykov, V. J. N. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.003 · Cited by 592
Self-citationThe thioredoxin system in cancer
Arnér, E. S. J., & Holmgren, A. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.10.009 · Cited by 589
The role of p53 in cancer drug resistance and targeted chemotherapy
Hientz, K., Mohr, A., Bhakta-Guha, D., & Efferth, T. (2016) · Oncotarget · doi:10.18632/oncotarget.13475 · Cited by 612
The expanding universe of p53 targets
Menendez, D., Inga, A., & Resnick, M. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2730 · Cited by 568
The Myc oncoprotein as a therapeutic target for human cancer
Vita, M. F., & Arsenian‐Henriksson, M. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.07.015 · Cited by 575
Targeting mutant p53 for cancer therapy: direct and indirect strategies
Hu, J., Cao, J., Topatana, W., Juengpanich, S., Li, S., Zhang, B., Shen, J., Cai, L., Cai, X., & Chen, M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01169-0 · Cited by 576
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517
Understanding the complexity of p53 in a new era of tumor suppression
Liu, Y., Su, Z., Tavana, O., & Gu, W. J. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.009 · Cited by 538
Genetically engineered mouse models in oncology research and cancer medicine
Kersten, K., de Visser, K. E., van Miltenburg, M. H., & Jonkers, J. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201606857 · Cited by 502
Solomon, J. M., Pasupuleti, R., Xu, L., McDonagh, T., Curtis, R., DiStefano, P. S., & Huber, L. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.28-38.2006 · Cited by 490
The p53 Pathway in Glioblastoma
Zhang, Y., Dube, C., Gibert, M., Cruickshanks, N., Wang, B., Coughlan, M., Yang, Y., Setiady, I., Deveau, C., Saoud, K., et al. (2018) · Cancers · doi:10.3390/cancers10090297 · Cited by 440
Dissecting p53-dependent apoptosis
Chipuk, J. E., & Green, D. R. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401908 · Cited by 462
Regulating tumor suppressor genes: post-translational modifications
Chen, L., Liu, S., & Tao, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0196-9 · Cited by 449
Oncogene addiction: setting the stage for molecularly targeted cancer therapyPreprint
Sharma, S. V., & Settleman, J. E. (2007) · Genes & Development · doi:10.1101/gad.1609907 · Cited by 451
Pro-senescence therapy for cancer treatment
Nardella, C., Clohessy, J. G., Alimonti, A., & Pandolfi, P. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3057 · Cited by 437
A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition
Kim, N. H., Kim, H. S., Li, X.-Y., Lee, I., Choi, H.-S., Kang, S. E., Cha, S. Y., Ryu, J. K., Yoon, D., Fearon, E. R., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201103097 · Cited by 445
Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer
Liu, G., Pei, F., Yang, F., Li, L., Amin, A. D., Liu, S., Buchan, J. R., & Cho, W. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020367 · Cited by 430
Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers
Wang, Y., & Deng, B. (2023) · Cancer and Metastasis Reviews · doi:10.1007/s10555-023-10084-4 · Cited by 439
Maier, P., Hartmann, L., Wenz, F. K., & Herskind, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17010102 · Cited by 449
Lehmann, S., Bykov, V. J. N., Ali, D., Andrén, O., Cherif, H., Tidefelt, U., Uggla, B., Yachnin, J., Juliusson, G., Moshfegh, A., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.7783 · Cited by 406
Self-citationChemosensitivity linked to p73 function
Irwin, M. S., Kondo, K., Marín, M. C., Cheng, L. S., Hahn, W. C., & Kaelin, W. G. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00078-3 · Cited by 406
Mitochondria-mediated apoptosis in mammals
Xiong, S., Mu, T., Wang, G., & Jiang, X. (2014) · Protein & Cell · doi:10.1007/s13238-014-0089-1 · Cited by 410
TP53 Mutations in Nonsmall Cell Lung Cancer
Mogi, A., & Kuwano, H. (2011) · BioMed Research International · doi:10.1155/2011/583929 · Cited by 404
Oršolić, N. (2011) · Cancer and Metastasis Reviews · doi:10.1007/s10555-011-9339-3 · Cited by 390
p53mutations in colorectal cancer- molecular pathogenesis and pharmacological reactivation
Li, X.-L. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i1.84 · Cited by 384
Enhanced Radiation Sensitivity in HPV-Positive Head and Neck Cancer
Kimple, R. J., Smith, M. A., Blitzer, G. C., Torres, A. D., Martin, J. A., Yang, R., Peet, C. R., Lorenz, L. D., Nickel, K. P., Klingelhutz, A. J., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0587 · Cited by 366
Mutant p53 as a target for cancer treatment
Duffy, M. J., Synnott, N. C., & Crown, J. P. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2017.06.023 · Cited by 369
The Tumor Suppressor p53: From Structures to Drug DiscoveryPreprint
Joerger, A. C., & Fersht, A. R. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000919 · Cited by 380
Strategies for reversing drug resistance
Fojo, T., & Bates, S. E. (2003) · Oncogene · doi:10.1038/sj.onc.1206951 · Cited by 358
Targeting p53 for the treatment of cancer
Duffy, M. J., Synnott, N. C., O’Grady, S., & Crown, J. P. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.07.005 · Cited by 355
Cell-cycle dysregulation and anticancer therapy
Stewart, Z. A., Westfall, M. D., & Pietenpol, J. A. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00026-9 · Cited by 343
A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas
Soragni, A., Janzen, D. M., Johnson, L. M., Lindgren, A. G., Thai-Quynh Nguyen, A., Tiourin, E., Soriaga, A. B., Lu, J., Jiang, L., Faull, K. F., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2015.12.002 · Cited by 341
Gain-of-function mutant p53 in cancer progression and therapy
Zhang, C., Liu, J., Xu, D., Zhang, T., Hu, W., & Feng, Z. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa040 · Cited by 358
The role of p53 in chemosensitivity and radiosensitivity
El‐Deiry, W. S. (2003) · Oncogene · doi:10.1038/sj.onc.1206949 · Cited by 337
Targeting Oncogenic Mutant p53 for Cancer Therapy
Parrales, A., & Iwakuma, T. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00288 · Cited by 345
Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy
Yue, X., Zhao, Y., Xu, Y., Zheng, M., Feng, Z., & Hu, W. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.03.030 · Cited by 308
Allele-Specific p53 Mutant Reactivation
Yu, X., Vázquez, A., Levine, A. J., & Carpizo, D. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.042 · Cited by 321
Kong, N., Tao, W., Ling, X., Wang, J., Xiao, Y., Shi, S., Ji, X., Shajii, A., Gan, S. T., Kim, N. Y., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw1565 · Cited by 314
Hermisson, M., Klumpp, A., Wick, W., Wischhusen, J., Nagel, G., Roos, W. P., Kaina, B., & Weller, M. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03583.x · Cited by 318
Soussi, T., & Wiman, K. G. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2015.53 · Cited by 305
Self-citationPharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription
Chipuk, J. E., Maurer, U., Green, D. R., & Schüler, M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00272-1 · Cited by 302
Sur, S., Pagliarini, R. A., Bunz, F., Rago, C., Diaz, L. A., Kinzler, K. W., Vogelstein, B., & Papadopoulos, N. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813333106 · Cited by 293
Dysregulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities
Plati, J., Bucur, O., & Khosravi‐Far, R. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21707 · Cited by 301
Targeting the Vulnerability of Glutathione Metabolism in ARID1A-Deficient Cancers
Ogiwara, H., Takahashi, K., Sasaki, M., Kuroda, T., Yoshida, H., Watanabe, R., Maruyama, A., Makinoshima, H., Chiwaki, F., Sasaki, H., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2018.12.009 · Cited by 292
p53 Family and Cellular Stress Responses in Cancer
Pflaum, J., Schlosser, S., & ller, M. M. ⁄. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00285 · Cited by 309
The rebel angel: mutant p53 as the driving oncogene in breast cancer
Walerych, D., Napoli, M., Collavin, L., & Sal, G. D. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs232 · Cited by 301
Mitra, A. P., Datar, R. H., & Côté, R. J. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.08.2073 · Cited by 289
Apoptosis-based therapies and drug targets
Fischer, U., & Schulze‐Osthoff, K. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401556 · Cited by 283
The p53 network: cellular and systemic DNA damage responses in cancer and aging
Vaddavalli, P. L., & Schumacher, B. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.02.010 · Cited by 304
To die or not to die: how does p53 decide?
Slee, E. A., O’Connor, D. J., & Lü, X. (2004) · Oncogene · doi:10.1038/sj.onc.1207516 · Cited by 282
Abuetabh, Y., Wu, H. H., Chai, C., Yousef, H. A., Persad, S., Sergi, C. M., & Leng, R. P. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00863-4 · Cited by 280
Farnebo, M., Bykov, V. J. N., & Wiman, K. G. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.152 · Cited by 272
Self-citationXiao, Y., Chen, J., Zhou, H., Zeng, X., Ruan, Z., Pu, Z., Jiang, X., Matsui, A., Zhu, L., Amoozgar, Z., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28279-8 · Cited by 269
APR-246 reactivates mutant p53 by targeting cysteines 124 and 277
Zhang, Q., Bykov, V. J. N., Wiman, K. G., & Zawacka-Pankau, J. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0463-7 · Cited by 261
Self-citationCargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study
Andaloussi, S. E., Järver, P., Johansson, H. J., & Langel, Ü. (2007) · Biochemical Journal · doi:10.1042/bj20070507 · Cited by 270
Vousden, K. H., & Prives, C. L. (2005) · Cell · doi:10.1016/j.cell.2004.12.027 · Cited by 259
New Approaches and Therapeutics Targeting Apoptosis in Disease
Fischer, U., & Schulze‐Osthoff, K. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.2.6 · Cited by 259
Smoking, p53 Mutation, and Lung Cancer
Gibbons, D. L., Byers, L. A., & Kurie, J. M. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0539 · Cited by 255
Gali‐Muhtasib, H. U., Diab‐Assaf, M., Boltze, C., Al-Hmaira, J., Hartig, R., Roessner, A., & Schneider‐Stock, R. (2004) · International Journal of Oncology · doi:10.3892/ijo.25.4.857 · Cited by 257
PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis
Bykov, V. J. N., Zache, N., Stridh, H., Westman, J., Bergman, J., Selivanova, G., & Wiman, K. G. (2005) · Oncogene · doi:10.1038/sj.onc.1208419 · Cited by 252
Self-citationTargeting p53 for Novel Anticancer Therapy
Wang, Z., & Sun, Y. (2010) · Translational Oncology · doi:10.1593/tlo.09250 · Cited by 256
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
Reactivation of Mutant p53 and Induction of Apoptosis in Human Tumor Cells by Maleimide Analogs
Bykov, V. J. N., Issaeva, N., Zache, N., Shilov, A., Hultcrantz, M., Bergman, J., Selivanova, G., & Wiman, K. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501664200 · Cited by 247
Self-citationMutant p53 in cancer therapy—the barrier or the path
Zhou, X. Y., Hao, Q., & Lu, H. (2018) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjy072 · Cited by 249
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
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
MYC in Oncogenesis and as a Target for Cancer Therapies
Albihn, A., Johnsen, J. I., & Arsenian‐Henriksson, M. (2010) · Advances in cancer research · doi:10.1016/s0065-230x(10)07006-5 · Cited by 246
p53 and Nur77/TR3 – transcription factors that directly target mitochondria for cell death induction
Moll, U. M., Marchenko, N. D., & Zhang, X.-K. (2006) · Oncogene · doi:10.1038/sj.onc.1209601 · Cited by 241
Mutant p53 in breast cancer: potential as a therapeutic target and biomarker
Duffy, M. J., Synnott, N. C., & Crown, J. P. (2018) · Breast Cancer Research and Treatment · doi:10.1007/s10549-018-4753-7 · Cited by 239
Waarts, M. R., Stonestrom, A. J., Park, Y. C., & Levine, R. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154943 · Cited by 249
A contradictory treatment for lysosomal storage disorders: inhibitors enhance mutant enzyme activity
Fan, J. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00158-5 · Cited by 232
p53 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
Computational identification of a transiently open L1/S3 pocket for reactivation of mutant p53
Wassman, C. D., Baronio, R., Demir, Ö., Wallentine, B. D., Chen, C.-K., Hall, L., Salehi, F., Lin, D., Chung, B. P., Hatfield, G. W., et al. (2013) · Nature Communications · doi:10.1038/ncomms2361 · Cited by 226
Metadata
- Authors
- Bykov, V. J. N., Issaeva, N., Shilov, A., Hultcrantz, M., Pugacheva, E., Chumakov, P., Bergman, J., Wiman, K. G., & Selivanova, G.
- Affiliations
- Karolinska University Hospital (SE)
- Engelhardt Institute of Molecular Biology (RU)
- Karolinska Institutet (SE)
- Corresponding author
- Wiman, Klas G.
- ORCID
- Venue
- Nature Medicine
- Published
- 2002-03
- Volume
- 8
- Issue
- 3
- Pages
- 282-288
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2092902276
- Cited by
- 1,067
- References
- 32
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 42 · 2023: 51 · 2022: 49 · 2021: 58 · 2020: 55 · 2019: 53 · 2018: 51 · 2017: 34 · 2016: 53 · 2015: 42 · 2014: 51 · 2013: 38 · 2012: 37
- FWCI
- 18.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mutant p53, PRIMA-1, p53 reactivation, tumor suppressor function, apoptosis, transcriptional activation, small molecules, anticancer drug development, DNA binding, p53 conformation, anticancer activity
- MeSH terms
- Animals, Antineoplastic Agents, Aza Compounds, Cell Separation, Flow Cytometry, Humans, Molecular Weight, Mutation, Neoplasms, Organic Chemicals, Protein Conformation, Transplantation, Heterologous, Tumor Cells, Cultured, Molecular Structure, Transcriptional Activation, Tumor Suppressor Protein p53, Apoptosis, Genes, Reporter, Bridged Bicyclo Compounds, Heterocyclic, In Situ Nick-End Labeling, Mice
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
