Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction

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 · see citing works

Surfing the p53 network

Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · 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

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 3,177 · see citing works

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 · see citing works

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 · see citing works

Inhibiting the p53–MDM2 interaction: an important target for cancer therapy

Chène, P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc991 · Cited by 765 · see citing works

Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction

Ding, K., Lu, Y., Nikolovska-Coleska, Z., Wang, G., Qiu, S., Shangary, S., Gao, W., Qin, D., Stuckey, J., Krajewski, K., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm051122a · Cited by 702 · see citing works

Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition

Shangary, S., Qin, D., McEachern, D., Liu, M., Miller, R. S., Qiu, S., Nikolovska-Coleska, Z., Ding, K., Wang, G., Chen, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708917105 · Cited by 660 · see citing works

Structure-based design of potent non-peptide MDM2 inhibitors

Ding, K., Lu, Y., Nikolovska-Coleska, Z., Qiu, S., Ding, Y., Gao, W., Stuckey, J., Krajewski, K., Roller, P. P., Tomita, Y., et al. (2005) · Journal of the American Chemical Society · doi:10.1021/ja051147z · Cited by 657 · see citing works

Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy

Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623 · see citing works

MDM2 inhibitors for cancer therapy

Vassilev, L. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.002 · Cited by 532 · see citing works

Discovery and Cocrystal Structure of Benzodiazepinedione HDM2 Antagonists That Activate p53 in Cells

Grasberger, B. L., Lu, T., Schubert, C., Parks, D. J., Carver, T. E., Koblish, H. K., Cummings, M. D., LaFrance, L. V., Milkiewicz, K. L., Calvo, R. R., et al. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049137g · Cited by 433 · see citing works

Targeting the MDM2-p53 Interaction for Cancer Therapy

Shangary, S. K., & Wang, S. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5136 · Cited by 364 · see citing works

Discovery of Potent Antagonists of the Interaction between Human Double Minute 2 and Tumor Suppressor p53

Garcı́a-Echeverrı́a, C., Chêne, P., Blommers, M. J. J., & Furet, P. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990966p · Cited by 246 · see citing works

p53 Activation by Small Molecules: Application in Oncology

Vassilev, L. T. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm058174k · Cited by 172 · see citing works

Small-Molecule Inhibitors of the MDM2-p53 Protein−Protein Interaction Based on an Isoindolinone Scaffold

Hardcastle, I. R., Ahmed, S. U., Atkins, H., Farnie, G., Golding, B. T., Griffin, R. J., Guyenne, S., Hutton, C., Källblad, P., Kemp, S. J., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0601194 · Cited by 149 · see citing works

Small Molecule Inhibitors of the MDM2-p53 Interaction Discovered by Ensemble-Based Receptor Models

Bowman, A. L., Nikolovska‐Coleska, Z., Zhong, H. A., Wang, S., & Carlson, H. A. (2007) · Journal of the American Chemical Society · doi:10.1021/ja073687x · Cited by 127 · see citing works

Discovery of a Nanomolar Inhibitor of the Human Murine Double Minute 2 (MDM2)−p53 Interaction through an Integrated, Virtual Database Screening Strategy

Lu, Y., Nikolovska‐Coleska, Z., Fang, X., Gao, W., Shangary, S. K., Qiu, S., Qin, D., & Wang, S. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060023+ · Cited by 115 · see citing works

Comprehensive biomarker and genomic analysis identifies p53 status as the major determinant of response to MDM2 inhibitors in chronic lymphocytic leukemia

Saddler, C. M., Ouillette, P. D., Kujawski, L. A., Shangary, S. K., Talpaz, M., Kaminski, M. S., Erba, H. P., Shedden, K., Wang, S., & Malek, S. N. (2007) · Blood · doi:10.1182/blood-2007-09-112698 · Cited by 96 · see citing works

Reactivation of p53 by a specific MDM2 antagonist (MI-43) leads to p21-mediated cell cycle arrest and selective cell death in colon cancer

Shangary, S., Ding, K., Qiu, S., Nikolovska-Coleska, Z., Bauer, J. A., Liu, M., Wang, G., Lu, Y., McEachern, D., Bernard, D., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0140 · Cited by 91 · see citing works

A Nonpeptidic Sulfonamide Inhibits the p53−mdm2 Interaction and Activates p53-Dependent Transcription in mdm2-Overexpressing Cells

Galatin, P. S., & Abraham, D. J. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm034182u · Cited by 90 · see citing works

Discovery of RG7388, a Potent and Selective p53–MDM2 Inhibitor in Clinical Development

Ding, Q., Zhang, Z., Liu, J.-J., Jiang, N., Zhang, J., Ross, T. M., Chu, X.-J., Bartkovitz, D., Podlaski, F., Janson, C., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400487c · Cited by 595 · see citing works

Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

Zhao, Y., Aguilar, A., Bernard, D., & Wang, S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501092z · Cited by 462 · see citing works

Discovery of AMG 232, a Potent, Selective, and Orally Bioavailable MDM2–p53 Inhibitor in Clinical Development

Sun, D., Li, Z., Rew, Y., Gribble, M., Bartberger, M. D., Beck, H. P., Canon, J., Chen, A., Chen, X., Chow, D., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401753e · Cited by 290 · see citing works

Diastereomeric 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 · see citing works

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 · see citing works

Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials

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 · see citing works

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 · see citing works

State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors

Sheng, C., Dong, G., Miao, Z., Zhang, W., & Wang, W. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00252d · Cited by 165 · see citing works

Discovery of a Small Molecule MDM2 Inhibitor (AMG 232) for Treating Cancer

Rew, Y., & Sun, D. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500627s · Cited by 125 · see citing works

Rational Design and Binding Mode Duality of MDM2–p53 Inhibitors

Gonzalez-Lopez de Turiso, F., Sun, D., Rew, Y., Bartberger, M. D., Beck, H. P., Canon, J., Chen, A., Chow, D., Correll, T. L., Huang, X., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400293z · Cited by 82 · see citing works

Targeting the MDM2-p53 protein–protein interaction for new cancer therapeutics

Wang, S., Zhao, Y., Bernard, D., Aguilar, A., & Kumar, S. (2012) · Topics in Medicinal Chemistry · doi:10.1007/978-3-642-28965-1_2 · Cited by 72 · see citing works

High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: a cytogenomic microarray analysis of 47 cases

Ricciotti, R. W., Baraff, A. J., Jour, G., Kyriss, M., Wu, Y., Liu, Y., Li, S.-C., Hoch, B., & Liu, Y. J. (2017) · Cancer Genetics · doi:10.1016/j.cancergen.2017.09.005 · Cited by 67 · see citing works

Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy

Zhang, Z., Ding, Q., Liu, J.-J., Zhang, J., Jiang, N., Chu, X.-J., Bartkovitz, D., Luk, K.-C., Janson, C., Tovar, C., et al. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.05.072 · Cited by 60 · see citing works

Inhibition of P53-murine double minute 2 (MDM2) interactions with 3,3′-spirocyclopentene oxindole derivatives

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

Restoration of p53 using the novel MDM2-p53 antagonist APG115 suppresses dedifferentiated papillary thyroid cancer cells

Chen, H., Luo, D., Zhang, L., Lin, X., Luo, Q., Yi, H., Wang, J., Yan, X., Li, B., Chen, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17398 · Cited by 29 · see citing works

Evaluating dose-limiting toxicities of MDM2 inhibitors in patients with solid organ and hematologic malignancies: a systematic review of the literature

Pi, L., Rooprai, J., Allan, D., Atkins, H., Bredeson, C., Fulcher, A., Ito, C., Ramsay, T., Shorr, Stanford, W., et al. (2019) · Leukemia Research · doi:10.1016/j.leukres.2019.106222 · Cited by 25 · see citing works

Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm

Hurevich, M., Swed, A., Joubran, S., et al. (2010) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2010.04.053 · Cited by 13 · see citing works

Synthesis, topoisomerase I inhibition and structure–activity relationship study of 2,4,6-trisubstituted pyridine derivatives

Zhao, L., Moon, Y., Basnet, A., et al. (2004) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2003.11.084 · Cited by 95 · see citing works

Molecular docking and structure–activity relationship studies on benzothiazole based non-peptidic BACE-1 inhibitors

Xu, W., Chen, G., Zhu, W., et al. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.08.111 · Cited by 23 · see citing works

Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors containing a stereochemically unique peptide isostere

Holmes, D. S., Bethell, R. C., Cammack, N. C., et al. (1993) · Journal of Medicinal Chemistry · doi:10.1021/jm00073a012 · Cited by 24 · see citing works

Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1α (HIF-1α) inhibitors

Kim, H. S., Hong, M., Lee, S.-C., Lee, H., Suh, Y., Oh, D., Seo, J. H., Choi, H., Kim, J. Y., Kim, K.-W., et al. (2015) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2015.09.033 · Cited by 28 · see citing works