Discovery of a Dihydroisoquinolinone Derivative (NVP-CGM097): A Highly Potent and Selective MDM2 Inhibitor Undergoing Phase 1 Clinical Trials in p53wt Tumors

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139 · see citing works

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484 · see citing works

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 · see citing works

p53, guardian of the genome

Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138 · 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

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 pathway: positive and negative feedback loops

Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967 · see citing works

Modes of p53 regulation.

Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610 · see citing works

Physiochemical drug properties associated with in vivo toxicological outcomes

Hughes, J. D., Blagg, J., Price, D. A., Bailey, S., DeCrescenzo, G. A., Devraj, R. V., Ellsworth, E. L., Fobian, Y. M., Gibbs, M. E., Gilles, R. W., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.071 · Cited by 995 · see citing works

A General and Efficient Copper Catalyst for the Amidation of Aryl Halides

Klapars, A., Huang, X. S., & Buchwald, S. L. (2002) · Journal of the American Chemical Society · doi:10.1021/ja0260465 · Cited by 855 · see citing works

The p53–Mdm2 module and the ubiquitin system

Michael, D., & Oren, M. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00099-8 · Cited by 759 · 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

Reduction of p53 gene dosage does not increase initiation or promotion but enhances malignant progression of chemically induced skin tumors

Kemp, C. J., Donehower, L. A., Bradley, A., & Balmain, A. (1993) · Cell · doi:10.1016/0092-8674(93)90461-x · Cited by 453 · see citing works

New and Original pKa Prediction Method Using Grid Molecular Interaction Fields

Milletti, F., Storchi, L., Sforna, G., & Cruciani, G. (2007) · Journal of Chemical Information and Modeling · doi:10.1021/ci700018y · Cited by 311 · 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

Mutational spectrum of p53 mutations in primary breast and ovarian tumors

Feki, A., & Irminger-Finger, I. (2004) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2004.07.002 · Cited by 139 · 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

The central valine concept provides an entry in a new class of non peptide inhibitors of the p53–MDM2 interaction

Furet, P., Chêne, P., Pover, A. D., Stachyra, T., Lisztwan, J. H., Kallen, J. A., & Masuya, K. (2012) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2012.03.083 · Cited by 73 · see citing works

Asymmetric Synthesis of the Protoberberine Alkaloid (S)-(−)-Xylopinine Using Enantiopure Sulfinimines

Davis, F. A., & Mohanty, P. K. (2002) · The Journal of Organic Chemistry · doi:10.1021/jo010988v · Cited by 62 · see citing works

Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53–MDM2 interaction with a distinct binding mode

Gessier, F., Kallen, J. A., Jacoby, E., Chêne, P., Stachyra, T., Ruetz, S., Jeay, S., Holzer, P., Masuya, K., & Furet, P. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.06.058 · Cited by 59 · see citing works

Rhodium-catalyzed addition of arylstannanes to carbon–heteroatom double bond

Ôi, S., Moro, M., Fukuhara, H., Kawanishi, T., & Inoue, Y. (2003) · Tetrahedron · doi:10.1016/s0040-4020(03)00586-6 · Cited by 58 · see citing works

Tetra-substituted imidazoles as a new class of inhibitors of the p53–MDM2 interaction

Vaupel, A., Bold, G., Pover, A. D., Stachyra, T., Lisztwan, J. H., Kallen, J. A., Masuya, K., & Furet, P. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.03.039 · Cited by 37 · see citing works

Knowledge-Based Virtual Screening: Application to the MDM4/p53 Protein–Protein Interaction

Jacoby, E., Boettcher, A., Mayr, L. M., Brown, N., Jenkins, J. L., Kallen, J. A., Engeloch, C., Schopfer, U., Furet, P., Masuya, K., et al. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-274-2_7 · Cited by 20 · see citing works

p53–MDM2 and MDMX Antagonists

Neochoritis, C. G., Estrada‐Ortiz, N., Khoury, K., & Dömling, A. S. S. (2014) · Annual reports in medicinal chemistry · doi:10.1016/b978-0-12-800167-7.00012-2 · Cited by 16 · see citing works

Recent disclosures of clinical candidates. Highlights from the Society of Medicines Research Symposium, held December 4, 2014 - National Heart & Lung Institute, London, UK

Collingwood, S. P., Ratcliffe, A. J., Pryde, D. C., & Porter, R. (2015) · Drugs of the Future · doi:10.1358/dof.2015.040.01.2273384 · Cited by 7 · see citing works

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 · see citing works

Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials

Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · see citing works

Tumor biomarkers for diagnosis, prognosis and targeted therapy

Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 772 · 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

MDM2 inhibition: an important step forward in cancer therapy

Konopleva, M. Y., Martinelli, G., Daver, N. G., Papayannidis, C., Wei, A. H., Higgins, B., Ott, M., Mascarenhas, J. O., & Andreeff, M. (2020) · Leukemia · doi:10.1038/s41375-020-0949-z · Cited by 376 · see citing works

Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression

Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312 · see citing works

Targeting the MDM2–p53 Protein–Protein Interaction for New Cancer Therapy: Progress and Challenges

Wang, S., Zhao, Y., Aguilar, A., Bernard, D., & Yang, C.-Y. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026245 · Cited by 300 · see citing works

Inhibitors of protein–protein interactions (PPIs): an analysis of scaffold choices and buried surface area

Xu, R., & Gestwicki, J. E. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.06.004 · Cited by 262 · see citing works

MDM2/X inhibitors under clinical evaluation: perspectives for the management of hematological malignancies and pediatric cancer

Tisato, V., Voltan, R., Gonelli, A., Secchiero, P., & Zauli, G. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0500-5 · Cited by 255 · 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

Ubiquitin ligases: guardians of mammalian development

Walma, D. A. C., Chen, Z., Bullock, A. N., & Yamada, K. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00448-5 · Cited by 212 · see citing works

Discovery of 4-((3′ <i>R</i> ,4′ <i>S</i> ,5′ <i>R</i> )-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development

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 · see citing works

From Discovery to Bedside: Targeting the Ubiquitin System

Wertz, I. E., & Wang, X. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.10.022 · Cited by 157 · see citing works

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

Krepler, C., Sproesser, K., Brafford, P. A., Beqiri, M., Garman, B., Xiao, M., Shannan, B., Watters, A. K., Perego, M., Zhang, G., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.021 · Cited by 151 · see citing works

MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future

Wang, W., Albadari, N. G., Du, Y., Fowler, J. F., Sang, H. T., Xian, W., McKeon, F., Li, W., Zhou, J., & Zhang, R. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.001026 · Cited by 147 · see citing works

The past, present and future of potential small-molecule drugs targeting p53-MDM2/MDMX for cancer therapy

Liu, Y., Wang, X., Wang, G., Yang, Y., Yuan, Y., & Ouyang, L. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.05.018 · Cited by 133 · see citing works

Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas

Todoric, J., Antonucci, L., Caro, G. D., Li, N., Wu, X., Lytle, N. K., Dhar, D., Banerjee, S., Fagman, J. B., Browne, C. D., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.10.011 · Cited by 129 · see citing works

Evolution of In Silico Strategies for Protein-Protein Interaction Drug Discovery

Macalino, S. J. Y., Basith, S., Clavio, N. A. B., Chang, H., Kang, S., & Choi, S. (2018) · Molecules · doi:10.3390/molecules23081963 · Cited by 113 · 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

Small-molecule MDM2 inhibitors in clinical trials for cancer therapy

Wang, S., & Chen, F. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114334 · Cited by 102 · see citing works

How To Design a Successful p53–MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures

Estrada‐Ortiz, N., Neochoritis, C. G., & Dömling, A. S. S. (2015) · ChemMedChem · doi:10.1002/cmdc.201500487 · Cited by 100 · see citing works

Unraveling the Guardian: p53’s Multifaceted Role in the DNA Damage Response and Tumor Treatment Strategies

Zhang, H., Xu, J., Long, Y., Maimaitijiang, A., Su, Z., Li, W., & Li, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312928 · Cited by 93 · see citing works

Targeting MDM2 for novel molecular therapy: Beyond oncology

Wang, W., Qin, J., Rajaei, M., Li, X., Yu, X., Hunt, C., & Zhang, R. (2019) · Medicinal Research Reviews · doi:10.1002/med.21637 · Cited by 90 · see citing works

Targeting Biomolecular Condensation and Protein Aggregation against Cancer

Silva, J. L., Foguel, D., Ferreira, V. F., Vieira, T. C. R. G., Marques, M. A., Ferretti, G. D. S., Outeiro, T. F., Cordeiro, Y., & de Oliveira, G. A. P. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00131 · Cited by 85 · see citing works

Medicinal Chemistry Strategies to Disrupt the p53–MDM2/MDMX Interaction

Lemos, A., Leão, M., Soares, J., Palmeira, A., Pinto, M. M. M., Saraiva, L., & Sousa, M. E. (2016) · Medicinal Research Reviews · doi:10.1002/med.21393 · Cited by 83 · see citing works

Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors

LaPlante, G., & Zhang, W. (2021) · Cancers · doi:10.3390/cancers13123079 · Cited by 82 · see citing works

Discovery of a novel class of highly potent inhibitors of the p53–MDM2 interaction by structure-based design starting from a conformational argument

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 &amp; Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.08.010 · Cited by 80 · see citing works

Reviving the guardian of the genome: Small molecule activators of p53

Nguyen, D., Liao, W., Zeng, S. X., & Lu, H. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.03.013 · Cited by 80 · see citing works

Therapeutic Approaches Targeting Nucleolus in Cancer

Carotenuto, P., Pecoraro, A., Palma, G., Russo, G., & Russo, A. (2019) · Cells · doi:10.3390/cells8091090 · Cited by 80 · see citing works

Prolonged Idasanutlin (RG7388) Treatment Leads to the Generation of p53-Mutated Cells

Skalniak, Ł., Kocik-Krol, J., Polak, J., Skalniak, A., Rak, M., Wolnicka-Głubisz, A., & Holak, T. A. (2018) · Cancers · doi:10.3390/cancers10110396 · Cited by 76 · see citing works

Targeted Degradation of MDM2 as a New Approach to Improve the Efficacy of MDM2-p53 Inhibitors

Wurz, R. P., & Cee, V. J. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01945 · Cited by 75 · see citing works

Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?

Hároníková, L., Bonczek, O., Zatloukalová, P., Kokas, F. Z., Kucerikova, M., Coates, P. J., Fåhræus, R., & Vojtěšek, B. (2021) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00293-6 · Cited by 71 · see citing works

Potent effect of the MDM2 inhibitor AMG232 on suppression of glioblastoma stem cells

Her, N.-G., Oh, J.-W., Oh, Y. J., Han, S., Cho, H. J., Lee, Y., Ryu, G. H., & Nam, D.-H. (2018) · Cell Death &amp; Disease · doi:10.1038/s41419-018-0825-1 · Cited by 68 · see citing works

PROTAC degraders with ligands recruiting MDM2 E3 ubiquitin ligase: an updated perspective

Han, X., Wei, W., & Sun, Y. (2022) · Acta Materia Medica · doi:10.15212/amm-2022-0010 · Cited by 67 · see citing works

MDM2: current research status and prospects of tumor treatment

Yao, Y., Zhang, Q., Li, Z., & Zhang, H. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03356-8 · Cited by 66 · see citing works

Role of p53 circuitry in tumorigenesis: A brief review

Niazi, S., Purohit, M., & Niazi, J. H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.08.099 · Cited by 65 · see citing works

MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer

Portman, N., Milioli, H. H., Alexandrou, S., Coulson, R. S., Yong, A., Fernandez, K. J., Chia, K. M., Halilovic, E., Segara, D., Parker, A., et al. (2020) · Breast Cancer Research · doi:10.1186/s13058-020-01318-2 · Cited by 65 · see citing works

Resistance mechanisms to TP53-MDM2 inhibition identified by in vivo piggyBac transposon mutagenesis screen in an Arf ^−/− mouse model

Chapeau, E. A., Gembarska, A., Durand, E. Y., Mandon, E., Estadieu, C., Romanet, V., Wiesmann, M., Tiedt, R., Lehar, J., de Weck, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620262114 · Cited by 64 · see citing works

Precisely controlled preparation of an advanced Na 3 V 2 (PO 4 ) 2 O 2 F cathode material for sodium ion batteries: the optimization of electrochemical properties and electrode kinetics

Gu, Z., Guo, J., Yang, Y., Yu, H., Xi, X., Zhao, X.-X., Guan, H., He, X., & Wu, X. (2019) · Inorganic Chemistry Frontiers · doi:10.1039/c8qi01374h · Cited by 64 · see citing works

The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy

Liao, G., Yang, D., Ma, L., Li, W., Hu, L., Zeng, L., Wu, P., Duan, L., & Liu, Z. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.044 · Cited by 63 · see citing works

The role of the MDM2/p53 axis in antitumor immune responses

Brummer, T., & Zeiser, R. (2023) · Blood · doi:10.1182/blood.2023020731 · Cited by 63 · see citing works

Small‐Molecule Stabilization of the 14‐3‐3/Gab2 Protein–Protein Interaction (PPI) Interface

Bier, D., Bartel, M., Sies, K., Halbach, S., Higuchi, Y., Haranosono, Y., Brummer, T., Kato, N., & Ottmann, C. (2015) · ChemMedChem · doi:10.1002/cmdc.201500484 · Cited by 61 · see citing works

Recent Small-Molecule Inhibitors of the p53–MDM2 Protein–Protein Interaction

Beloglazkina, A. A., Zyk, N. V., Majouga, A. G., & Beloglazkina, E. K. (2020) · Molecules · doi:10.3390/molecules25051211 · Cited by 59 · see citing works

Molecular Docking and Molecular Dynamics Studies Reveal the Anticancer Potential of Medicinal-Plant-Derived Lignans as MDM2-P53 Interaction Inhibitors

Shoaib, T. H., Abdelmoniem, N., Mukhtar, R. M., Alqhtani, A. T., Alalawi, A. L., Alawaji, R., Althubyani, M. S., Mohamed, S. G. A., Mohamed, G. A., Ibrahim, S. R. M., et al. (2023) · Molecules · doi:10.3390/molecules28186665 · Cited by 59 · see citing works

Studying protein–protein interactions: Latest and most popular approaches

Akbarzadeh, S., Coşkun, Ö., & Günçer, B. (2024) · Journal of Structural Biology · doi:10.1016/j.jsb.2024.108118 · Cited by 58 · see citing works

Conformational control in structure-based drug design

Zheng, Y., Tice, C. M., & Singh, S. B. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.04.079 · Cited by 58 · see citing works

Dysregulation of the Ubiquitin Proteasome System in Human Malignancies: A Window for Therapeutic Intervention

Fhu, C. W., & Ali, A. (2021) · Cancers · doi:10.3390/cancers13071513 · Cited by 57 · see citing works

Decoding the messaging of the ubiquitin system using chemical and protein probes

Henneberg, L. T., & Schulman, B. A. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.03.009 · Cited by 52 · see citing works

Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein–Protein Interactions

Zhang, S., Lou, J., Li, Y., Zhou, F., Yan, Z., Lyu, X., & Zhao, Y. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c00940 · Cited by 47 · see citing works

Helping the released guardian: Drug combinations for supporting the anticancer activity of HDM2 (MDM2) antagonists

Kocik, J., Machula, M., Wisniewska, A., Surmiak, E., Holak, T. A., & Skalniak, L. (2019) · Cancers · doi:10.3390/cancers11071014 · Cited by 46 · see citing works

A balancing act: using small molecules for therapeutic intervention of the p53 pathway in cancer

Miller, J. J., Gaiddon, C., & Storr, T. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00163e · Cited by 46 · see citing works

MDM2- and FLT3-inhibitors in the treatment of <i>FLT3</i>-ITD acute myeloid leukemia, specificity and efficacy of NVP-HDM201 and midostaurin

Seipel, K., Marques, M. A. T., Sidler, C., Mueller, B. U., & Pabst, T. (2018) · Haematologica · doi:10.3324/haematol.2018.191650 · Cited by 45 · see citing works

A therapeutic patent overview of MDM2/X-targeted therapies (2014–2018)

Skalniak, Ł., Surmiak, E., & Holak, T. A. (2019) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2019.1582645 · Cited by 45 · see citing works

Asymmetric catalysis with chiral cyclopentadienyl complexes to access privileged scaffolds

Davies, C., Shaaban, S., & Waldmann, H. (2022) · Trends in Chemistry · doi:10.1016/j.trechm.2022.01.005 · Cited by 44 · see citing works

Emerging Pharmacotherapeutic Strategies to Overcome Undruggable Proteins in Cancer

Lu, Y., Yang, Y., Zhu, G., Zeng, H., Fan, Y., Guo, F., Xu, D., Wang, B., Chen, D., & Ge, G. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.83026 · Cited by 41 · see citing works

Small molecules that target the ubiquitin system

Wu, H. Q., Baker, D. A., & Ovaa, H. (2020) · Biochemical Society Transactions · doi:10.1042/bst20190535 · Cited by 41 · see citing works

Targetable Pathways in the Treatment of Retroperitoneal Liposarcoma

Casadei, L., de Faria, F. C. C., Lopez‐Aguiar, A. G., Pollock, R. E., & Grignol, V. P. (2022) · Cancers · doi:10.3390/cancers14061362 · Cited by 41 · 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

Pharmacokinetic–pharmacodynamic guided optimisation of dose and schedule of CGM097, an HDM2 inhibitor, in preclinical and clinical studies

Bauer, S., Demetri, G. D., Halilovic, E., Dummer, R., Meille, C., Tan, D. S.-W., Guerreiro, N., Jullion, A., Ferretti, S., Jeay, S., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01444-4 · Cited by 37 · see citing works

p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with structural insights and SAR studies

Chahat, Bhatia, R., & Kumar, B. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.115020 · Cited by 36 · see citing works

A rational blueprint for the design of chemically-controlled protein switches

Shui, S., Gaínza, P., Scheller, L., Yang, C., Kurumida, Y., Rosset, S., Georgeon, S., Roberto, R. B. D., Castellanos-Rueda, R., Reddy, S. T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25735-9 · Cited by 35 · see citing works

Small Molecule Modulators of RING-Type E3 Ligases: MDM and Cullin Families as Targets

Bulatov, E., Zagidullin, A. A., Valiullina, A., Sayarova, R., & Rizvanov, A. A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00450 · Cited by 33 · see citing works

Promising new therapeutic targets for regulation of inflammation and immunity: RING-type E3 ubiquitin ligases

Bulatov, E., Valiullina, A., Sayarova, R., & Rizvanov, A. A. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.08.001 · Cited by 32 · see citing works

Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting

Tan, Y. S., Mhoumadi, Y., & Verma, C. S. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz009 · Cited by 32 · see citing works

Progress of small molecules for targeted protein degradation: PROTACs and other technologies

Zhao, H., Xin, M., & Zhang, S. (2023) · Drug Development Research · doi:10.1002/ddr.22026 · Cited by 31 · 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

Structural States of Hdm2 and HdmX: X‐ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes

Kallen, J. A., Izaac, A., Chau, S., Wirth, E., Schoepfer, J. G., Mah, R., Schlapbach, A., Stutz, S., Vaupel, A., Guagnano, V., et al. (2019) · ChemMedChem · doi:10.1002/cmdc.201900201 · Cited by 30 · see citing works

Targeting p53-MDM2 Interaction Using Small Molecule Inhibitors and the Challenges Needed to be Addressed

Zanjirband, M., & Rahgozar, S. (2019) · Current Drug Targets · doi:10.2174/1389450120666190402120701 · Cited by 29 · see citing works

Protein-protein interaction inhibitors: advances in anticancer drug design

Ferreira, L. L. G., Oliva, G., & Andricopulo, A. D. (2016) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2016.1223038 · Cited by 29 · see citing works

Recent Synthetic Approaches towards Small Molecule Reactivators of p53

Silva, J. L., Lima, C. G. S., Rangel, L. P., Ferretti, G. D. S., Pauli, F. P., Ribeiro, R. C. B., Silva, T. B., da Silva, F. D. C., & Ferreira, V. F. (2020) · Biomolecules · doi:10.3390/biom10040635 · Cited by 28 · see citing works

Hazardous Shortcuts in Standard Binding Free Energy Calculations

Blazhynska, M., Goulard Coderc de Lacam, E., Chen, H., Roux, B., & Chipot, C. (2022) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.2c01490 · Cited by 27 · see citing works

Therapeutic Strategies to Activate p53

Aguilar, A., & Wang, S. (2022) · Pharmaceuticals · doi:10.3390/ph16010024 · Cited by 27 · see citing works

Cross Talk Networks of Mammalian Target of Rapamycin Signaling With the Ubiquitin Proteasome System and Their Clinical Implications in Multiple Myeloma.

Eichner, R., Fernández-Sáiz, V., Targosz, B., & Bassermann, F. (2019) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2018.06.001 · Cited by 21 · see citing works

Transcription Factors and Cancer

Shiah, J. V., Johnson, D. E., & Grandis, J. R. (2023) · The Cancer Journal · doi:10.1097/ppo.0000000000000639 · Cited by 26 · see citing works

Medicinal Chemistry of Inhibiting RING-Type E3 Ubiquitin Ligases

Blaquière, N., Villemure, E., & Staben, S. T. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01451 · Cited by 26 · see citing works

Evolution in non-peptide α-helix mimetics on the road to effective protein-protein interaction modulators

Algar, S., Martín‐Martinez, M., & González‐Muñiz, R. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113015 · Cited by 26 · see citing works

Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds

Liu, L., He, B., Miles, J. A., Wang, W., Mao, Z., Che, W. I., Lu, J., Chen, X., Wilson, A. J., Ma, D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7369 · Cited by 26 · 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

Discovery of novel polycyclic spiro-fused carbocyclicoxindole-based anticancer agents

Zhang, L., Ren, W. T., Wang, X., Zhang, J., Liu, J., Zhao, L., & Zhang, X. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.12.021 · Cited by 25 · see citing works

The HDM2 (MDM2) Inhibitor NVP-CGM097 Inhibits Tumor Cell Proliferation and Shows Additive Effects with 5-Fluorouracil on the p53-p21-Rb-E2F1 Cascade in the p53wild type Neuroendocrine Tumor Cell Line GOT1

Reuther, C., Heinzle, V., Nölting, S., Herterich, S., Hahner, S., Halilovic, E., Jeay, S., Wuerthner, J., Prada, E. T. A., Spöttl, G., et al. (2016) · Neuroendocrinology · doi:10.1159/000453369 · Cited by 24 · see citing works

p53: An Attractive Therapeutic Target for Cancer

Patel, K. R., & Patel, H. D. (2019) · Current Medicinal Chemistry · doi:10.2174/1573406415666190621094704 · Cited by 24 · see citing works

Roles of posttranslational modifications in lipid metabolism and cancer progression

Feng, T., Zhang, H., Zhou, Y., Zhu, Y., Shi, S., Li, K., Lin, P., & Chen, J. (2024) · Biomarker Research · doi:10.1186/s40364-024-00681-y · Cited by 23 · see citing works

NVP-CGM097, an HDM2 Inhibitor, Antagonizes ATP-Binding Cassette Subfamily B Member 1-Mediated Drug Resistance

Zhang, M., Chen, X.-Y., Dong, X.-D., Wang, J., Feng, W., Teng, Q., Cui, Q., Li, J., Li, X., & Chen, Z. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01219 · Cited by 23 · see citing works

Discovery of JN122, a Spiroindoline-Containing Molecule that Inhibits MDM2/p53 Protein–Protein Interaction and Exerts Robust In Vivo Antitumor Efficacy

Cheng, J., Yan, Z., Jiang, K., Liu, C., Xu, D., Lyu, X., Hu, X., Zhang, S., Zhou, Y., Li, J., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01815 · Cited by 22 · see citing works

In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor

Vaupel, A., Holzer, P., Ferretti, S., Guagnano, V., Kallen, J. A., Mah, R., Masuya, K., Ruetz, S., Rynn, C., Schlapbach, A., et al. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.08.027 · Cited by 22 · see citing works

Targeted Brain Tumor Therapy by Inhibiting the MDM2 Oncogene: In Vitro and In Vivo Antitumor Activity and Mechanism of Action

Punganuru, S. R., Arutla, V., Zhao, W., Rajaei, M., Deokar, H. S., Zhang, R., Buolamwini, J. K., Srivenugopal, K. S., & Wang, W. (2020) · Cells · doi:10.3390/cells9071592 · Cited by 22 · see citing works

Targeted modulation of E3 ligases using engineered ubiquitin variants

LeBlanc, N., Mallette, E., & Zhang, W. (2020) · FEBS Journal · doi:10.1111/febs.15536 · Cited by 22 · see citing works

Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy

Jiang, Y., Ni, S., Xiao, B., & Jia, L. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.07.019 · Cited by 21 · see citing works

Reductive ipso-radical cyclization onto aromatic rings of five-membered alicyclic amino acids bearing N-(2-phenyl)benzoyl groups by photoinduced electron transfer promoted decarboxylation

Yamada, T., Ozaki, Y., Yamawaki, M., Sugiura, Y., Nishino, K., Morita, T., & Yoshimi, Y. (2017) · Tetrahedron Letters · doi:10.1016/j.tetlet.2017.01.038 · Cited by 21 · see citing works

Absolute Binding Free Energy Calculations for Highly Flexible Protein MDM2 and Its Inhibitors

Singh, N., & Li, W. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134765 · Cited by 21 · see citing works

Unraveling the Role of TP53 in Colorectal Cancer Therapy: From Wild-Type Regulation to Mutant

Li, W., Li, L., Yang, H., Shi, C., Lei, Z., Guo, L., & Wang, Y. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2907272 · Cited by 20 · see citing works

Bioorthogonal Probes for the Study of MDM2‐p53 Inhibitors in Cells and Development of High‐Content Screening Assays for Drug Discovery

D’Alessandro, P. L., Buschmann, N., Kaufmann, M., Furet, P., Baysang, F., Brunner, R., Marzinzik, A. L., Vorherr, T. E., Stachyra, T., Ottl, J., et al. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201608568 · Cited by 20 · see citing works

Metal-Free Synthesis of N-Aryl-Substituted Azacycles from Cyclic Ethers Using POCl3

La, M. T., Kang, S., & Kim, H. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.9b00377 · Cited by 20 · see citing works

Cross-coupling of 2-methylquinolines and in-situ activated isoquinolines: Construction of 1,2-disubstituted isoquinolinones

Shi, J., Zeng, Z., Xu, S., Cai, Z., Luo, Y., Fan, Y., Zhu, Z., Wen, T., & Chen, X. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.02.032 · Cited by 20 · see citing works

Discovery, X-ray structure and CPP-conjugation enabled uptake of p53/MDM2 macrocyclic peptide inhibitors

Schneider, A. F. L., Kallen, J. A., Ottl, J., Reid, P., Ripoche, S., Ruetz, S., Stachyra, T., Hintermann, S., Dumelin, C. E., Hackenberger, C. P. R., et al. (2021) · RSC Chemical Biology · doi:10.1039/d1cb00056j · Cited by 19 · see citing works

Targeting protein-protein interactions with low molecular weight and short peptide modulators: insights on disease pathways and starting points for drug discovery

Trisciuzzi, D., Villoutreix, B. O., Siragusa, L., Baroni, M., Cruciani, G., & Nicolotti, O. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2218641 · Cited by 19 · see citing works

Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer

Bhatia, N., Khator, R., Kulkarni, S., Singh, Y., Kumar, P., & Thareja, S. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867330666221114103924 · Cited by 18 · see citing works

Discovery of Novel p53-MDM2 Inhibitor (RG7388)-Conjugated PlatinumIV Complexes as Potent Antitumor Agents

Liu, W., Ma, Y., He, Y., Liu, Y., Guo, Z., He, J., Han, X., Hu, Y., Li, M., Jiang, R., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00784 · Cited by 18 · see citing works

Harnessing p53 for targeted cancer therapy: new advances and future directions

Andrysík, Z., & Espinosa, J. M. (2025) · Transcription · doi:10.1080/21541264.2025.2452711 · Cited by 18 · see citing works

Targeting MDMX and PKCδ to improve current uveal melanoma therapeutic strategies

Heijkants, R. C., Nieveen, M. C., Hart, K. C. ’., Teunisse, A. F. A. S., & Jochemsen, A. G. (2018) · Oncogenesis · doi:10.1038/s41389-018-0041-y · Cited by 18 · see citing works

Discovery of Potent and Selective p53-MDM2 Protein–Protein Interaction Inhibitors as Anticancer Drugs

Holzer, P. (2017) · CHIMIA International Journal for Chemistry · doi:10.2533/chimia.2017.716 · Cited by 28 · see citing works

Abstract 1797: Discovery of NVP-CGM097, a highly potent and optimized small molecule inhibitor of Mdm2 under evaluation in a Phase I clinical trial

Jeay, S., Berghausen, J., Buschmann, N., Chêne, P., Cozens, R. M., Erdmann, D., Ferretti, S., Furet, P., Gabriel, T., Gessier, F., et al. (2014) · Cancer Research · doi:10.1158/1538-7445.am2014-1797 · Cited by 4 · see citing works

Discovery of a novel class of highly potent inhibitors of the p53–MDM2 interaction by structure-based design starting from a conformational argument

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 &amp; Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.08.010 · Cited by 80 · see citing works

In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor

Vaupel, A., Holzer, P., Ferretti, S., Guagnano, V., Kallen, J. A., Mah, R., Masuya, K., Ruetz, S., Rynn, C., Schlapbach, A., et al. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.08.027 · Cited by 22 · see citing works

Mechanistic study of NVP-CGM097: A potent, selective and species specific inhibitor of p53-Mdm2

Valat, M. T. (2015) · Drug Designing Open Access · doi:10.4172/2169-0138.s1.008 · Cited by 8 · see citing works