Clinical Overview of MDM2/X-Targeted Therapies
Open accessAbstract
MDM2 and MDMX are the primary negative regulators of p53, which under normal conditions maintain low intracellular levels of p53 by targeting it to the proteasome for rapid degradation and inhibiting its transcriptional activity. Both MDM2 and MDMX function as powerful oncogenes and are commonly over-expressed in some cancers, including sarcoma (~20%) and breast cancer (~15%). In contrast to tumors that are p53 mutant, whereby the current therapeutic strategy restores the normal active conformation of p53, MDM2 and MDMX represent logical therapeutic targets in cancer for increasing wild-type (WT) p53 expression and activities. Recent preclinical studies suggest that there may also be situations that MDM2/X inhibitors could be used in p53 mutant tumors. Since the discovery of nutlin-3a, the first in a class of small molecule MDM2 inhibitors that binds to the hydrophobic cleft in the N-terminus of MDM2, preventing its association with p53, there is now an extensive list of related compounds. In addition, a new class of stapled peptides that can target both MDM2 and MDMX have also been developed. Importantly, preclinical modeling, which has demonstrated effective in vitro and in vivo killing of WT p53 cancer cells, has now been translated into early clinical trials allowing better assessment of their biological effects and toxicities in patients. In this overview, we will review the current MDM2- and MDMX-targeted therapies in development, focusing particularly on compounds that have entered into early phase clinical trials. We will highlight the challenges pertaining to predictive biomarkers for and toxicities associated with these compounds, as well as identify potential combinatorial strategies to enhance its anti-cancer efficacy.
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MDM2 and MDMX act as negative regulators of p53, maintaining p53 at low level by binding to N-terminal and mediating degradation in normal cells.
“Both Murine double minute 2 (MDM2, HMD2 in human) and MDMX act as negative regulators of p53, maintaining p53 at a low level by directly binding to its N-terminal and mediating its degradation in normal cells.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [215]
MDM2, the most important negative regulator of p53, directly binds to p53 and forms complexes with it, regulating the stability and activity of p53 protein.
“MDM2, the most important negative regulator of p53, directly binds to p53 and forms complexes with it, regulating the stability and activity of p53 protein.215”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [215]
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Cites
Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal
Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. (2013) · Science Signaling · doi:10.1126/scisignal.2004088 · Cited by 15,160 · see citing works
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661 · see citing works
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Self-citationRegulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · see citing works
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 · see citing works
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 · see citing works
MDM2, MDMX and p53 in oncogenesis and cancer therapy
Wade, M., Li, Y.-C., & Wahl, G. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3430 · Cited by 1,279 · cited 1× · see citing works
“Other potential off-target effects on MDM2 inhibitors include the loss of its ability to ubiquitinate other proteins, such as the steroid hormone receptors [estrogen receptor (ER) and androgen receptor (AR)] and Rb, as well as interference with MDM2’s role in DNA repair and modifying chromatin structure (58).”
BackgroundStott, F. J., Bates, S., James, M. C., McConnell, B. B., Starborg, M., Brookes, S., Palmero, I., Ryan, K. M., Hara, E., Vousden, K. H., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5001 · Cited by 1,165 · see citing works
Haupt, S., Berger, M., Goldberg, Z., & Haupt, Y. (2003) · Journal of Cell Science · doi:10.1242/jcs.00739 · Cited by 1,136 · see citing works
Self-citationp53 ubiquitination: Mdm2 and beyond
Brooks, C. L., & Gu, W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.020 · Cited by 924 · see citing works
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804 · cited 2× · see citing works
“Despite the similarity in the N-terminal p53-binding domain of MDM2 and MDMX, most of these small molecule inhibitors bind with significantly less avidity to MDMX and are therefore primarily MDM2 specific (12).”
BackgroundSmall molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors
Issaeva, N., Bozko, P. M., Enge, M., Protopopova, M., Verhoef, L. G. G. C., Masucci, M. G., Pramanik, A., & Selivanova, G. (2004) · Nature Medicine · doi:10.1038/nm1146 · Cited by 749 · see citing works
Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
Honda, R., & Yasuda, H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.1.22 · Cited by 724 · see citing works
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 723 · see citing works
Modeling the Therapeutic Efficacy of p53 Restoration in Tumors
Martins, C. P., Brown-Swigart, L., & Evan, G. I. (2006) · Cell · doi:10.1016/j.cell.2006.12.007 · Cited by 600 · see citing works
Ray-Coquard, I., Blay, J.-Y., Italiano, A., Le Cesne, A., Penel, N., Zhi, J., Heil, F., Rueger, R., Graves, B., Ding, M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70474-6 · Cited by 571 · see citing works
Proliferation of aneuploid human cells is limited by a p53-dependent mechanism
Thompson, S. L., & Compton, D. A. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200905057 · Cited by 494 · see citing works
Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth
Zhu, J., Sammons, M. A., Donahue, G., Dou, Z., Vedadi, M., Getlik, M., Barsyte-Lovejoy, D., Al-awar, R., Katona, B. W., Shilatifard, A., et al. (2015) · Nature · doi:10.1038/nature15251 · Cited by 493 · see citing works
Posttranslational Modification of p53: Cooperative Integrators of FunctionPreprint
Meek, D. W., & Anderson, C. W. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a000950 · Cited by 487 · see citing works
Tetraploid State Induces p53-dependent Arrest of Nontransformed Mammalian Cells in G1
Andreassen, P. R., Lohez, O. D., Lacroix, F., & Margolis, R. L. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.5.1315 · Cited by 429 · see citing works
Complex structure and regulation of the P16 (MTS1) locus.
Stone, S., Jiang, P., Dayananth, P., Tavtigian, S. V., Katcher, H. L., Parry, D., Peters, G., & Kamb, A. (1995) · PubMed · Cited by 383 · see citing works
Results of the Phase I trial of RG7112, a small-molecule MDM2 antagonist in leukemia
Andreeff, M., Kelly, K. R., Yee, K., Assouline, S., Strair, R., Popplewell, L., Bowen, D., Martinelli, G., Drummond, M. W., Vyas, P., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0481 · Cited by 352 · see citing works
Two-phase dynamics of p53 in the DNA damage response
Zhang, X.-P., Liu, F., & Wang, W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100600108 · Cited by 333 · see citing works
Mao, L., Merlo, A. U., Bedi, G. C., Shapiro, G. I., Edwards, C. D., Rollins, B. J., & Sidransky, D. (1995) · PubMed · Cited by 329 · see citing works
The p53-p21-DREAM-CDE/CHR pathway regulates G 2 /M cell cycle genes
Fischer, M., Quaas, M., Steiner, L., & Engeland, K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv927 · Cited by 324 · see citing works
Dong, P., Karaayvaz, M., Jia, N., Kaneuchi, M., Hamada, J., Watari, H., Sudo, S., Ju, J., & Sakuragi, N. (2012) · Oncogene · doi:10.1038/onc.2012.334 · Cited by 307 · see citing works
Tovar, C., Graves, B., Packman, K., Filipovic, Z., Xia, B. H. M., Tardell, C., Garrido, R., Lee, E., Kolinsky, K., To, K.-H., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2807 · Cited by 283 · see citing works
Differential Activation of Target Cellular Promoters by p53 Mutants with Impaired Apoptotic Function
Ludwig, R. L., Bates, S., & Vousden, K. H. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4952 · Cited by 275 · see citing works
A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis.
Kracikova, M., Akiri, G., George, A., Sachidanandam, R., & Aaronson, S. A. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.155 · Cited by 261 · see citing works
Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells <i>in vivo</i>
Francoz, S., Froment, P., Bogaerts, S., De Clercq, S., Maetens, M., Doumont, G., Bellefroid, E., & Marine, J.-C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508476103 · Cited by 260 · see citing works
Zhou, G., Wang, J., Zhao, M., Xie, T., Tanaka, N., Sano, D., Patel, A. A., Ward, A. M., Sandulache, V. C., Jasser, S. A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.04.024 · Cited by 241 · see citing works
MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin
Hu, B., Gilkes, D. M., Farooqi, B., Sebti, S. M., & Chen, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c600147200 · Cited by 236 · see citing works
Popowicz, G. M., Czarna, A., Wolf, S., Wang, K., Wang, W., Dömling, A. S. S., & Holak, T. A. (2010) · Cell Cycle · doi:10.4161/cc.9.6.10956 · Cited by 232 · see citing works
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 · cited 1× · see citing works
“In addition, several small molecule inhibitors, which bind specifically to the N-terminus of MDMX, have recently been developed and are currently undergoing preclinical testing (25, 26).”
BackgroundLevels of HdmX expression dictate the sensitivity of normal and transformed cells to Nutlin-3
Patton, J. T., Mayo, L. D., Singhi, A. D., Gudkov, A. V., Stark, G. R., & Jackson, M. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3832 · Cited by 189 · see citing works
Brooks, C. L., & Gu, W. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.05.022 · Cited by 186 · see citing works
Mutant p53 reactivation by small molecules makes its way to the clinic
Bykov, V. J. N., & Wiman, K. G. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.04.017 · Cited by 180 · see citing works
Limiting the power of p53 through the ubiquitin proteasome pathwayPreprint
Pant, V., & Lozano, G. (2014) · Genes & Development · doi:10.1101/gad.247452.114 · Cited by 165 · see citing works
Hdmx modulates the outcome of p53 activation in human tumor cells
Wade, M., Wong, E. T., Tang, M., Stommel, J. M., & Wahl, G. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605405200 · Cited by 163 · see citing works
Mutant p53 stimulates chemoresistance of pancreatic adenocarcinoma cells to gemcitabine
Fiorini, C., Cordani, M., Padroni, C., Blandino, G., Agostino, S. D., & Donadelli, M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.10.003 · Cited by 144 · see citing works
Estrogen receptor prevents p53-dependent apoptosis in breast cancer
Bailey, S. T., Shin, H., Westerling, T., Liu, X. S., & Brown, M. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018858109 · Cited by 142 · see citing works
Ubiquitin-independent p53 proteasomal degradation
Tsvetkov, P., Reuven, N. B., & Shaul, Y. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.67 · Cited by 134 · see citing works
Acquisition of p53 mutations in response to the non-genotoxic p53 activator Nutlin-3
Aziz, M. H., Shen, H., & Maki, C. G. (2011) · Oncogene · doi:10.1038/onc.2011.185 · Cited by 131 · see citing works
MDM2 and MDMX: Alone and together in regulation of p53.
Shadfan, M., Lopez-Pajares, V., & Yuan, Z.-M. (2012) · PubMed · Cited by 125 · see citing works
Gain-of-function mutant p53 upregulates CXC chemokines and enhances cell migration
Yeudall, W. A., Vaughan, C. A., Miyazaki, H., et al. (2011) · Carcinogenesis · doi:10.1093/carcin/bgr270 · Cited by 121 · see citing works
A Small-Molecule Inhibitor of MDMX Activates p53 and Induces Apoptosis
Wang, H., Ma, X., Ren, S., Buolamwini, J. K., & Yan, C. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0581 · Cited by 117 · see citing works
Zhang, S., Zhou, L., Hong, B., van den Heuvel, A. P. J., Prabhu, V. V., Warfel, N. A., Kline, C. L. B., Dicker, D. T., Kopelovich, L., & El‐Deiry, W. S. (2015) · Cancer Research · doi:10.1158/0008-5472.can-13-1079 · Cited by 106 · see citing works
Discovery of Mdm2-MdmX E3 Ligase Inhibitors Using a Cell-Based Ubiquitination Assay
Herman, A. G., Hayano, M., Poyurovsky, M. V., Shimada, K., Skouta, R., Prives, C., & Stockwell, B. R. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0104 · Cited by 100 · see citing works
Contribution of two independent MDM2-binding domains in p14ARF to p53 stabilization
Lohrum, M. A. E., Ashcroft, M. A., Kubbutat, M. H. G., & Vousden, K. H. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00472-3 · Cited by 91 · see citing works
A distinct p53 target gene set predicts for response to the selective p53–HDM2 inhibitor NVP-CGM097
Jeay, S., Gaulis, S., Ferretti, S., Bitter, H., Ito, M., Valat, T., Murakami, M., Ruetz, S., Guthy, D. A., Rynn, C., et al. (2015) · eLife · doi:10.7554/elife.06498 · Cited by 85 · see citing works
Chee, J. L. Y., Saidin, S., Lane, D. P., Leong, S. M., Noll, J. E., Neilsen, P. M., Phua, Y. T., Gabra, H., & Lim, T. M. (2013) · Cell Cycle · doi:10.4161/cc.23054 · Cited by 70 · see citing works
Kuribayashi, K., Finnberg, N. K., Jeffers, J. R., Zambetti, G. P., & El‐Deiry, W. S. (2011) · Cell Cycle · doi:10.4161/cc.10.14.16588 · Cited by 69 · see citing works
Not all p53 gain-of-function mutants are created equal
Mello, S. S., & Attardi, L. D. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.53 · Cited by 69 · see citing works
Huang, M. J., Zhang, H., Liu, T., Tian, D., Gu, L., & Zhou, M. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-0425 · Cited by 67 · see citing works
Rao, B., Laı́n, S., & Thompson, A. M. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.702 · Cited by 66 · see citing works
Reisman, D., Takahashi, P., Polson, A., & Boggs, K. (2012) · Biochemistry Research International · doi:10.1155/2012/808934 · Cited by 60 · see citing works
Leslie, P. L., Ke, H., & Zhang, Y. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.644435 · Cited by 50 · see citing works
Targeting the MDM2/MDM4 Interaction Interface as a Promising Approach for p53 Reactivation Therapy
Pellegrino, M., Mancini, F., Lucà, R., Coletti, A., Giacchè, N., Manni, I., Arisi, I., Florenzano, F., Teveroni, E., Buttarelli, M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0439 · Cited by 48 · see citing works
Identifying the determinants of response to MDM2 inhibition
Saiki, A. Y., Caenepeel, S. R., Cosgrove, E. J., Su, C., Boedigheimer, M. J., & Oliner, J. D. (2015) · Oncotarget · doi:10.18632/oncotarget.3116 · Cited by 39 · see citing works
Carrillo, A. M., Hicks, M., Khabele, D., & Eischen, C. M. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0089 · Cited by 31 · see citing works
Qin, J., Wang, W., Voruganti, S., Wang, H., Zhang, W., & Zhang, R. (2015) · Oncotarget · doi:10.18632/oncotarget.5851 · Cited by 28 · see citing works
Seo, S., Hwang, C.-S., Choe, T., Hong, S., Yi, J. Y., Hwang, S., Lee, H.-G., Oh, S. T., Lee, Y., & Park, I. (2014) · Oncotarget · doi:10.18632/oncotarget.3100 · Cited by 20 · see citing works
Sonkin, D. (2015) · eLife · doi:10.7554/elife.10279 · Cited by 20 · see citing works
Zhang, H., Gu, L., Liu, T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100960 · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906 · see citing works
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 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia
Carvajal, L. A., Neriah, D. B., Senecal, A., Benard, L., Thiruthuvanathan, V., Yatsenko, T., Narayanagari, S.-R., Wheat, J. C., Todorova, T. I., Mitchell, K., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao3003 · Cited by 249 · see citing works
Guo, G., Yu, M., Xiao, W., Celis, E., & Cui, Y. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2832 · Cited by 168 · see citing works
A Small Molecule Reacts with the p53 Somatic Mutant Y220C to Rescue Wild-type Thermal Stability
Guiley, K. Z., & Shokat, K. M. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0381 · Cited by 102 · see citing works
Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives
Fang, Y., Liao, G., & Yu, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.003 · Cited by 106 · see citing works
Furet, P., Masuya, K., Kallen, J., Stachyra-Valat, T., Ruetz, S., Guagnano, V., Holzer, P., Mah, R., Stutz, S., Vaupel, A., et al. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.08.010 · Cited by 80 · see citing works
Cornillie, J., Wozniak, A., Li, H., Gebreyohannes, Y. K., Wellens, J., Hompes, D., Debiec-Rychter, M., Sciot, R., & Schöffski, P. (2020) · Clinical and Translational Oncology · doi:10.1007/s12094-019-02158-z · Cited by 56 · see citing works
McCubrey, J. A., Yang, L. V., Abrams, S. L., Steelman, L. S., Follo, M. Y., Cocco, L., Ratti, S., Martelli, A. M., Augello, G., & Cervello, M. (2022) · Cells · doi:10.3390/cells11142155 · Cited by 49 · see citing works
MDM2/X inhibitors as radiosensitizers for glioblastoma targeted therapy
Miles, X., Vandevoorde, C., Hunter, A., & Bolcaen, J. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.703442 · Cited by 40 · see citing works
CDK4 inhibition diminishes p53 activation by MDM2 antagonists
Sriraman, A., Dickmanns, A., Najafova, Z., Johnsen, S. A., & Dobbelstein, M. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0968-0 · Cited by 40 · see citing works
Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides
Charoenpattarapreeda, J., Tan, Y. S., Iegre, J., Walsh, S. J., Fowler, E., Eapen, R. S., Wu, Y., Sore, H. F., Verma, C. S., Itzhaki, L., et al. (2019) · Chemical Communications · doi:10.1039/c9cc04022f · Cited by 35 · see citing works
Gicquel, M., Gomez, C., Garcia Alvarez, M. C., Pamlard, O., Guérineau, V., Jacquet, E., Bignon, J., Voituriez, A., & Marinetti, A. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01137 · Cited by 34 · see citing works
MDM2 inhibition in the treatment of glioblastoma: From concept to clinical investigation
Pellot Ortiz, K. I., Rechberger, J. S., Nonnenbroich, L. F., Daniels, D. J., & Sarkaria, J. N. (2023) · Biomedicines · doi:10.3390/biomedicines11071879 · Cited by 30 · see citing works
- Authors
- Burgess, A., Chia, K. M., Haupt, S., Thomas, D., Haupt, Y., & Lim, E.
- Affiliations
- Garvan Institute of Medical Research (AU)
- The University of Melbourne (AU)
- Corresponding author
- Lim, Elgene
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2016-01-27
- Volume
- 6
- Pages
- 7-7
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC4728205
- OpenAlex
- W2272978256
- Cited by
- 315
- References
- 64
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 17 · 2022: 26 · 2021: 32 · 2020: 44 · 2019: 48 · 2018: 59 · 2017: 48 · 2016: 10 · 2014: 2
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Institute NSW (10/FRL/3-02)
- National Health and Medical Research Council (APP1104364, APP9628426)
- National Breast Cancer Foundation (PRAC14-002)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- MDM2 inhibitors, p53, Nutlin-3a, stapled peptides, small molecule inhibitors, sarcoma, breast cancer, predictive biomarkers, drug toxicity, combination therapy, clinical trials
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 ›
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