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Review Article

MDM2/MDM2-p53相互作用抑制剂治疗癌症的最新进展

卷 30, 期 32, 2023

发表于: 27 December, 2022

页: [3668 - 3701] 页: 34

弟呕挨: 10.2174/0929867330666221114103924

价格: $65

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摘要

MDM2和MDM2-p53相互作用抑制剂的发现改变了抗癌研究的方向，因为它涉及全球约50%的癌症病例。不仅抑制MDM2，而且它与p53的相互作用被证明是抗癌药物设计和开发的有效策略。据报道，天然和合成来源的各种分子具有优异的MDM2抑制潜力。本文综述了MDM2-p53相互作用环的病理生理学和MDM2/MDM2-p53相互作用抑制剂的最新专利文献。重点还放在靶标活性位点的特征及其与目前fda批准的抑制剂的期望相互作用上。本文还阐述了先前报道的MDM2/MDM2-p53相互作用抑制剂的设计方法、它们的SAR研究、计算机研究以及来自天然和合成来源的各种抑制剂的生物学功效。试图涵盖最近获得专利的MDM2/MDM2- p53相互作用抑制剂。

关键词: 鼠类double minute 2 (MDM2)， p53，肿瘤，MDM2-p53抑制剂，nutlin，生物功效。

« Previous Next »
[1]
Bacher, G.; Beckers, T.; Emig, P.; Klenner, T.; Kutscher, B.; Nickel, B. New small molecule tubulin inhibitors. Pure Appl. Chem., 2001, 73(9), 1459-1464.
[http://dx.doi.org/10.1351/pac200173091459]
[2]
Saijo, N. Preclinical and clinical trials of topoisomerase inhibitors. Ann. N. Y. Acad. Sci., 2000, 922(1), 92-99.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb07028.x] [PMID: 11193928]
[3]
Verma, S.; Singh, A.; Mishra, A. Molecular dynamics investigation on the inhibition of MDM2-p53 interaction by polyphenols. Mol. Inform., 2013, 32(2), 203-212.
[http://dx.doi.org/10.1002/minf.201200113] [PMID: 27481281]
[4]
Vidal, A.; Koff, A. Cell-cycle inhibitors: Three families united by a common cause. Gene, 2000, 247(1-2), 1-15.
[http://dx.doi.org/10.1016/S0378-1119(00)00092-5] [PMID: 10773440]
[5]
Sharon Kemp; Brodie, C.R.; Collins, J.G.; Kemp, S.; Aldrich-Wright, J.R. DNA intercalators in cancer therapy: Organic and inorganic drugs and their spectroscopic tools of analysis. Mini Rev. Med. Chem., 2007, 7(6), 627-648.
[http://dx.doi.org/10.2174/138955707780859413] [PMID: 17584161]
[6]
Yu, W.; Simmons-Menchaca, M.; Gapor, A.; Sanders, B.G.; Kline, K. Induction of apoptosis in human breast cancer cells by tocopherols and tocotrienols. Nutr. Cancer, 1999, 33(1), 26-32.
[http://dx.doi.org/10.1080/01635589909514744] [PMID: 10227040]
[7]
Cahilly-Snyder, L.; Yang-Feng, T.; Francke, U.; George, D.L. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Somat. Cell Mol. Genet., 1987, 13(3), 235-244.
[http://dx.doi.org/10.1007/BF01535205] [PMID: 3474784]
[8]
Brooks, C.L.; Gu, W. p53 ubiquitination: MDM2 and beyond. Mol. Cell, 2006, 21(3), 307-315.
[http://dx.doi.org/10.1016/j.molcel.2006.01.020] [PMID: 16455486]
[9]
Momand, J.; Wu, H.H.; Dasgupta, G. MDM2 - master regulator of the p53 tumor suppressor protein. Gene, 2000, 242(1-2), 15-29.
[http://dx.doi.org/10.1016/S0378-1119(99)00487-4] [PMID: 10721693]
[10]
Chen, L.; Yin, H.; Farooqi, B.; Sebti, S.; Hamilton, A.D.; Chen, J. p53 α-Helix mimetics antagonize p53/MDM2 interaction and activate p53. Mol. Cancer Ther., 2005, 4(6), 1019-1025.
[http://dx.doi.org/10.1158/1535-7163.MCT-04-0342] [PMID: 15956260]
[11]
Wu, H.; Leng, R.P. UBE4B, a ubiquitin chain assembly factor, is required for MDM2-mediated p53 polyubiquitination and degradation. Cell Cycle, 2011, 10(12), 1912-1915.
[http://dx.doi.org/10.4161/cc.10.12.15882] [PMID: 21558803]
[12]
Oliner, J.D.; Saiki, A.Y.; Caenepeel, S. The role of MDM2 amplification and overexpression in tumorigenesis. Cold Spring Harb. Perspect. Med., 2016, 6(6), a026336.
[http://dx.doi.org/10.1101/cshperspect.a026336] [PMID: 27194168]
[13]
Strachan, T.; Read, A.P. Cancer Genetics. Human Molecular Genetics 2nd ed;Wiley-Liss: New York. 1999, pp, 427-444.
[14]
Levine, A.J.; Oren, M. The first 30 years of p53: Growing ever more complex. Nat. Rev. Cancer, 2009, 9(10), 749-758.
[http://dx.doi.org/10.1038/nrc2723] [PMID: 19776744]
[15]
Carr, M.I.; Jones, S.N. Regulation of the MDM2-p53 signaling axis in the DNA damage response and tumorigenesis. Transl. Cancer Res., 2016, 5(6), 707-724.
[http://dx.doi.org/10.21037/tcr.2016.11.75] [PMID: 28690977]
[16]
Hou, H.; Sun, D.; Zhang, X. The role of MDM2 amplification and overexpression in therapeutic resistance of malignant tumors. Cancer Cell Int., 2019, 19(1), 216.
[http://dx.doi.org/10.1186/s12935-019-0937-4] [PMID: 31440117]
[17]
Wade, M.; Li, Y.C.; Matani, A.S.; Braun, S.M.G.; Milanesi, F.; Rodewald, L.W.; Wahl, G.M. Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells. Oncogene, 2012, 31(45), 4789-4797.
[http://dx.doi.org/10.1038/onc.2011.625] [PMID: 22266850]
[18]
Blattner, C.; Hay, T.; Meek, D.W.; Lane, D.P. Hypophosphorylation of Mdm2 augments p53 stability. Mol. Cell. Biol., 2002, 22(17), 6170-6182.
[http://dx.doi.org/10.1128/MCB.22.17.6170-6182.2002] [PMID: 12167711]
[19]
Iwakuma, T.; Lozano, G. MDM2, an introduction. Mol. Cancer Res., 2003, 1(14), 993-1000.
[PMID: 14707282]
[20]
Michael, D. The p53–Mdm2 Module and the Ubiquitin System, Seminars in Cancer Biology; Elsevier; Amsterdam, 2003, pp. 49-58.
[21]
Gupta, A.; Shah, K.; Oza, M.J.; Behl, T. Reactivation of p53 gene by MDM2 inhibitors: A novel therapy for cancer treatment. Biomed. Pharmacother., 2019, 109, 484-492.
[http://dx.doi.org/10.1016/j.biopha.2018.10.155] [PMID: 30551517]
[22]
Peng, Y.; Chen, L.; Li, C.; Lu, W.; Chen, J. Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J. Biol. Chem., 2001, 276(44), 40583-40590.
[http://dx.doi.org/10.1074/jbc.M102817200] [PMID: 11507088]
[23]
May, P.; May, E. Twenty years of p53 research: Structural and functional aspects of the p53 protein. Oncogene, 1999, 18(53), 7621-7636.
[http://dx.doi.org/10.1038/sj.onc.1203285] [PMID: 10618702]
[24]
Chang, F.; Syrjänen, S.; Kurvinen, K.; Syrjänen, K. The p53 tumor suppressor gene as a common cellular target in human carcinogenesis. Am. J. Gastroenterol., 1993, 88(2), 174-186.
[PMID: 8424417]
[25]
Vousden, K.H.; Prives, C. Blinded by the light: The growing complexity of p53. Cell, 2009, 137(3), 413-431.
[http://dx.doi.org/10.1016/j.cell.2009.04.037] [PMID: 19410540]
[26]
Toufektchan, E.; Toledo, F. The guardian of the genome revisited: p53 downregulates genes required for telomere maintenance, DNA repair, and centromere structure. Cancers, 2018, 10(5), 135.
[http://dx.doi.org/10.3390/cancers10050135] [PMID: 29734785]
[27]
Momand, J.; Zambetti, G. P.; Olson, D. C.; George, D.; Levine, A. J. The MDM-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. cell, 1992, 69(7), 1237-1245.
[28]
Haupt, Y.; Maya, R.; Kazaz, A.; Oren, M. Mdm2 promotes the rapid degradation of p53. Nature, 1997, 387(6630), 296-299.
[http://dx.doi.org/10.1038/387296a0] [PMID: 9153395]
[29]
Leng, P.; Brown, D.R.; Shivakumar, C.V.; Deb, S.; Deb, S.P. N-terminal 130 amino acids of MDM2 are sufficient to inhibit p53-mediated transcriptional activation. Oncogene, 1995, 10(7), 1275-1282.
[PMID: 7731677]
[30]
Perry, M.E.; Piette, J.; Zawadzki, J.A.; Harvey, D.; Levine, A.J. The mdm-2 gene is induced in response to UV light in a p53-dependent manner. Proc. Natl. Acad. Sci. USA, 1993, 90(24), 11623-11627.
[http://dx.doi.org/10.1073/pnas.90.24.11623] [PMID: 8265599]
[31]
Shangary, S.; Wang, S. Targeting the MDM2-p53 interaction for cancer therapy. Clin. Cancer Res., 2008, 14(17), 5318-5324.
[http://dx.doi.org/10.1158/1078-0432.CCR-07-5136] [PMID: 18765522]
[32]
Sakurai, K.; Chung, H.S.; Kahne, D. Use of a retroinverso p53 peptide as an inhibitor of MDM2. J. Am. Chem. Soc., 2004, 126(50), 16288-16289.
[http://dx.doi.org/10.1021/ja044883w] [PMID: 15600307]
[33]
Van Maerken, T.; Vandesompele, J.; Rihani, A.; De Paepe, A.; Speleman, F. Escape from p53-mediated tumor surveillance in neuroblastoma: Switching off the p14ARF-MDM2-p53 axis. Cell Death Differ., 2009, 16(12), 1563-1572.
[http://dx.doi.org/10.1038/cdd.2009.138] [PMID: 19779493]
[34]
Zhao, Y.; Aguilar, A.; Bernard, D.; Wang, S. Small molecule inhibitors of the MDM2-p53 protein-protein interaction (MDM2 Inhibitors) in clinical trials for cancer treatment. J. Med. Chem., 2015, 58(3), 1038-1052.
[http://dx.doi.org/10.1021/jm501092z] [PMID: 25396320]
[35]
Lézard, L. Ascentage Pharma's MDM2-p53 inhibitor APG-115 (Alrizomadlin) granted an orphan drug designation by the FDA for the treatment of stage IIB-IV melanoma, marking the twelfth obtained by the company. Available from: https://www.prnewswire.com/news/ascentage-pharma/
[36]
Tolcher, A.W.; Reeves, J.A.; McKean, M.; Chmielowski, B.; Beck, J.T.; Shaheen, M.F.; Somaiah, N.; Wilson, M.; Spira, A.I.; Drabick, J.J.; Tang, Y.; Winkler, R.; Li, M.; Ahmad, M.; Lu, M.; Liang, Z.; Yang, D.; Zhai, Y. Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs. J. Clin. Oncol., 2021, 39(15 Suppl.), 2506.
[http://dx.doi.org/10.1200/JCO.2021.39.15_suppl.2506]
[37]
McKean, M.; Tolcher, A.W.; Reeves, J.A.; Chmielowski, B.; Shaheen, M.F.; Beck, J.T.; Orloff, M.M.; Somaiah, N.; Van Tine, B.A.; Drabick, J.J. Newly updated activity results of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, plus pembrolizumab: Phase 2 study in adults and children with various solid tumors. Am. Soc. Clin. Oncol., 2022, 40(16), 9517-9517.
[38]
Aguilar, A.; Lu, J.; Liu, L.; Du, D.; Bernard, D.; McEachern, D.; Przybranowski, S.; Li, X.; Luo, R.; Wen, B.; Sun, D.; Wang, H.; Wen, J.; Wang, G.; Zhai, Y.; Guo, M.; Yang, D.; Wang, S. Discovery of 4-((3′ R, 4′ S, 5′ R )-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. J. Med. Chem., 2017, 60(7), 2819-2839.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01665] [PMID: 28339198]
[39]
Kuznar, W. Unique immunotherapy combos evaluated in advanced melanoma. Target Ther Oncol, 2021, 10, 10.
[40]
Zhai, Y.; Wang, J. 450 Trial in progress: A phase 1b study of alrizomadlin, alone or plus 5-azacitidine or cytarabine, in pts with relapsed/refractory acute myeloid leukemia and relapsed higher-risk myelodysplastic syndrome. J. Immunother. Cancer, 2021, 9(Suppl. 2), A478-A478.
[http://dx.doi.org/10.1136/jitc-2021-SITC2021.450]
[41]
Wang, W.; Zhang, X.; Qin, J.J.; Voruganti, S.; Nag, S.A.; Wang, M.H.; Wang, H.; Zhang, R. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2. PLoS One, 2012, 7(7), e41586.
[http://dx.doi.org/10.1371/journal.pone.0041586] [PMID: 22911819]
[42]
Malloy, K.L.; Choi, H.; Fiorilla, C.; Valeriote, F.A.; Matainaho, T.; Gerwick, W.H. Hoiamide D, a marine cyanobacteria-derived inhibitor of p53/MDM2 interaction. Bioorg. Med. Chem. Lett., 2012, 22(1), 683-688.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.054] [PMID: 22104152]
[43]
Vogel, S.M.; Bauer, M.R.; Joerger, A.C.; Wilcken, R.; Brandt, T.; Veprintsev, D.B.; Rutherford, T.J.; Fersht, A.R.; Boeckler, F.M. Lithocholic acid is an endogenous inhibitor of MDM4 and MDM2. Proc. Natl. Acad. Sci. USA, 2012, 109(42), 16906-16910.
[http://dx.doi.org/10.1073/pnas.1215060109] [PMID: 23035244]
[44]
Huang, M.; Zhang, H.; Liu, T.; Tian, D.; Gu, L.; Zhou, M. Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol. Cancer Ther., 2013, 12(2), 184-194.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0425] [PMID: 23243057]
[45]
Dung, T.D.; Day, C.H.; Binh, T.V.; Lin, C.H.; Hsu, H.H.; Su, C.C.; Lin, Y.M.; Tsai, F.J.; Kuo, W.W.; Chen, L.M.; Huang, C.Y. PP2A mediates diosmin p53 activation to block HA22T cell proliferation and tumor growth in xenografted nude mice through PI3K–Akt–MDM2 signaling suppression. Food Chem. Toxicol., 2012, 50(5), 1802-1810.
[http://dx.doi.org/10.1016/j.fct.2012.01.021] [PMID: 22289577]
[46]
Jin, L.; Li, C.; Xu, Y.; Wang, L.; Liu, J.; Wang, D.; Hong, C.; Jiang, Z.; Ma, Y.; Chen, Q.; Yu, F. Epigallocatechin gallate promotes p53 accumulation and activity via the inhibition of MDM2-mediated p53 ubiquitination in human lung cancer cells. Oncol. Rep., 2013, 29(5), 1983-1990.
[http://dx.doi.org/10.3892/or.2013.2343] [PMID: 23483203]
[47]
Leão, M.; Gomes, S.; Pedraza-Chaverri, J.; Machado, N.; Sousa, E.; Pinto, M.; Inga, A.; Pereira, C.; Saraiva, L. Α-mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach. J. Nat. Prod., 2013, 76(4), 774-778.
[http://dx.doi.org/10.1021/np400049j] [PMID: 23540934]
[48]
Proietti, S.; Cucina, A.; Dobrowolny, G.; D’Anselmi, F.; Dinicola, S.; Masiello, M.G.; Pasqualato, A.; Palombo, A.; Morini, V.; Reiter, R.J.; Bizzarri, M. Melatonin down-regulates MDM2 gene expression and enhances p53 acetylation in MCF-7 cells. J. Pineal Res., 2014, 57(1), 120-129.
[http://dx.doi.org/10.1111/jpi.12150] [PMID: 24920214]
[49]
Tin, A.S.; Park, A.H.; Sundar, S.N.; Firestone, G.L. Essential role of the cancer stem/progenitor cell marker nucleostemin for indole-3-carbinol anti-proliferative responsiveness in human breast cancer cells. BMC Biol., 2014, 12(1), 72.
[http://dx.doi.org/10.1186/s12915-014-0072-6] [PMID: 25209720]
[50]
Qin, J.J.; Wang, W.; Voruganti, S.; Wang, H.; Zhang, W.D.; Zhang, R. Identification of a new class of natural product MDM2 inhibitor: In vitro and in vivo anti-breast cancer activities and target validation. Oncotarget, 2015, 6(5), 2623-2640.
[http://dx.doi.org/10.18632/oncotarget.3098] [PMID: 25739118]
[51]
Borah, D.; Gogoi, D.; Yadav, R.N.S. Computer aided screening, docking and ADME study of mushroom derived compounds as MDM2 inhibitor, a novel approach. Natl. Acad. Sci. Lett., 2015, 38(6), 469-473.
[http://dx.doi.org/10.1007/s40009-015-0366-4]
[52]
Leão, M.; Soares, J.; Gomes, S.; Raimundo, L.; Ramos, H.; Bessa, C.; Queiroz, G.; Domingos, S.; Pinto, M.; Inga, A.; Cidade, H.; Saraiva, L. Enhanced cytotoxicity of prenylated chalcone against tumour cells via disruption of the p53–MDM2 interaction. Life Sci., 2015, 142, 60-65.
[http://dx.doi.org/10.1016/j.lfs.2015.10.015] [PMID: 26475964]
[53]
Cominetti, M.M.D.; Goffin, S.A.; Raffel, E.; Turner, K.D.; Ramoutar, J.C.; O’Connell, M.A.; Howell, L.A.; Searcey, M. Identification of a new p53/MDM2 inhibitor motif inspired by studies of chlorofusin. Bioorg. Med. Chem. Lett., 2015, 25(21), 4878-4880.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.014] [PMID: 26115576]
[54]
Muhseen, Z.T.; Li, G. Promising terpenes as natural antagonists of cancer: An in-silico approach. Molecules, 2019, 25(1), 155.
[http://dx.doi.org/10.3390/molecules25010155] [PMID: 31906032]
[55]
Woo, S.M.; Choi, Y.K.; Kim, A.J.; Cho, S.G.; Ko, S.G. p53 causes butein-mediated apoptosis of chronic myeloid leukemia cells. Mol. Med. Rep., 2016, 13(2), 1091-1096.
[http://dx.doi.org/10.3892/mmr.2015.4672] [PMID: 26676515]
[56]
Qin, J-J.; Sarkar, S.; Voruganti, S.; Agarwal, R.; Wang, W.; Zhang, R. Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy. J. Biomed. Res., 2016, 30(4), 322-333.
[PMID: 27533941]
[57]
Qin, J.J.; Wang, W.; Sarkar, S.; Voruganti, S.; Agarwal, R.; Zhang, R. Inulanolide A as a new dual inhibitor of NFAT1-MDM2 pathway for breast cancer therapy. Oncotarget, 2016, 7(22), 32566-32578.
[http://dx.doi.org/10.18632/oncotarget.8873] [PMID: 27105525]
[58]
Verma, S.; Grover, S.; Tyagi, C.; Goyal, S.; Jamal, S.; Singh, A.; Grover, A. Hydrophobic interactions are a key to MDM2 inhibition by polyphenols as revealed by molecular dynamics simulations and MM/PBSA free energy calculations. PLoS One, 2016, 11(2), e0149014.
[http://dx.doi.org/10.1371/journal.pone.0149014] [PMID: 26863418]
[59]
Noguchi, T.; Oishi, S.; Honda, K.; Kondoh, Y.; Saito, T.; Ohno, H.; Osada, H.; Fujii, N. Screening of a virtual mirror-image library of natural products. Chem. Commun. (Camb.), 2016, 52(49), 7653-7656.
[http://dx.doi.org/10.1039/C6CC03114E] [PMID: 27198617]
[60]
Kong, Y.; Lu, Z.L.; Wang, J.J.; Zhou, R.; Guo, J.; Liu, J.; Sun, H.L.; Wang, H.; Song, W.; Yang, J.; Xu, H.X. Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene. Oncol. Rep., 2016, 36(3), 1447-1456.
[http://dx.doi.org/10.3892/or.2016.4935] [PMID: 27432230]
[61]
Singh, A.K.; Chauhan, S.S.; Singh, S.K.; Verma, V.V.; Singh, A.; Arya, R.K.; Maheshwari, S.; Akhtar, M.S.; Sarkar, J.; Rangnekar, V.M.; Chauhan, P.M.S.; Datta, D. Dual targeting of MDM2 with a novel small-molecule inhibitor overcomes TRAIL resistance in cancer. Carcinogenesis, 2016, 37(11), 1027-1040.
[http://dx.doi.org/10.1093/carcin/bgw088] [PMID: 27543608]
[62]
Jing, B.; Liu, M.; Yang, L.; Cai, H.; Chen, J.; Li, Z.; Kou, X.; Wu, Y.; Qin, D.; Zhou, L.; Jin, J.; Lei, H.; Xu, H.; Wang, W.; Wu, Y. Characterization of naturally occurring pentacyclic triterpenes as novel inhibitors of deubiquitinating protease USP7 with anticancer activity in vitro. Acta Pharmacol. Sin., 2018, 39(3), 492-498.
[http://dx.doi.org/10.1038/aps.2017.119] [PMID: 29168472]
[63]
Ishiba, H.; Noguchi, T.; Shu, K.; Ohno, H.; Honda, K.; Kondoh, Y.; Osada, H.; Fujii, N.; Oishi, S. Investigation of the inhibitory mechanism of apomorphine against MDM2–p53 interaction. Bioorg. Med. Chem. Lett., 2017, 27(11), 2571-2574.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.082] [PMID: 28400230]
[64]
Riaz, M.; Ashfaq, U.A.; Qasim, M.; Yasmeen, E.; Ul Qamar, M.T.; Anwar, F. Screening of medicinal plant phytochemicals as natural antagonists of p53–MDM2 interaction to reactivate p53 functioning. Anticancer Drugs, 2017, 28(9), 1032-1038.
[http://dx.doi.org/10.1097/CAD.0000000000000548] [PMID: 28723868]
[65]
Wang, W.; Qin, J.J.; Li, X.; Tao, G.; Wang, Q.; Wu, X.; Zhou, J.; Zi, X.; Zhang, R. Prevention of prostate cancer by natural product MDM2 inhibitor GS25: In vitro and in vivo activities and molecular mechanisms. Carcinogenesis, 2018, 39(8), 1026-1036.
[http://dx.doi.org/10.1093/carcin/bgy063] [PMID: 29762656]
[66]
Pawar, A.C. Targeting p53-MDM2 interaction by natural plant products: A novel approach for future cancer therapy. Int. J. Life Sci. Scienti. Res, 2017, 3(2), 940-950.
[67]
Gu, L.; Zhang, H.; Liu, T.; Draganov, A.; Yi, S.; Wang, B.; Zhou, M. Inhibition of MDM2 by a rhein-derived compound AQ-101 suppresses cancer development in SCID mice. Mol. Cancer Ther., 2018, 17(2), 497-507.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0566] [PMID: 29282301]
[68]
Akhtar, S.; Khan, M.K.A.; Arif, J.M. Evaluation and elucidation studies of natural aglycones for anticancer potential using apoptosis-related markers: An in silico study. Interdiscip. Sci., 2018, 10(2), 297-310.
[http://dx.doi.org/10.1007/s12539-016-0191-6] [PMID: 27709544]
[69]
Gong, H.; An, J.; Dong, Q.; Li, J.; Yang, W.; Sun, W.; Su, Z.; Zhang, S. Discovery of SCY45, a natural small-molecule MDM2-p53 interaction inhibitor. Chem. Biodivers., 2019, 16(6), cbdv.201900081.
[http://dx.doi.org/10.1002/cbdv.201900081] [PMID: 30989812]
[70]
Ilic, V.; Egorova, O.; Tsang, E.; Gatto, M.; Yi, W.; Zhao, Y.; Sheng, Y. Bioflavonoid Hinokiflavone is a novel MDM2 inhibitor. Available from: https://sciforum.net/manuscripts/9208/slides.pdf
[71]
Ilic, V.K. Investigating the Anti-Cancer Effects of Small Molecule MEI-1 as a Potential MDM2 Inhibitor. Master's Thesis, York University, Torento, Canada, 2021. Available from: https://yorkspace.library.yorku.ca/xmlui/handle/10315/38638
[72]
Verma, S.; Pandey, A.K. Epicatechin an incredible tool to dissociate MDM2-p53 interaction for treatment of glioblastomas: A molecular docking and molecular dynamics simulation approach. Netw. Model. Anal. Health Inform. Bioinform., 2021, 10(1), 6.
[http://dx.doi.org/10.1007/s13721-021-00286-7] [PMID: 34849327]
[73]
Liu, L.; Xu, Z.; Yu, B.; Tao, L.; Cao, Y. Berbamine inhibits cell proliferation and migration and induces cell death of lung cancer cells via regulating c-Maf, PI3K/Akt, and MDM2-P53 pathways. Evid.-Based Complement. Altern. Med., 2021, 2021, 5517143.
[74]
Huang, H.; Park, S.; Zhang, H.; Park, S.; Kwon, W.; Kim, E.; Zhang, X.; Jang, S.; Yoon, D.; Choi, S.K.; Yi, J.; Kim, S.; Dong, Z.; Lee, M.; Ryoo, Z.; Kim, M.O. Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo. J. Exp. Clin. Cancer Res., 2021, 40(1), 114.
[http://dx.doi.org/10.1186/s13046-021-01895-w] [PMID: 33785035]
[75]
Zhang, Z.; Chu, X.J.; Liu, J.J.; Ding, Q.; Zhang, J.; Bartkovitz, D.; Jiang, N.; Karnachi, P.; So, S.S.; Tovar, C.; Filipovic, Z.M.; Higgins, B.; Glenn, K.; Packman, K.; Vassilev, L.; Graves, B. Discovery of potent and orally active p53-MDM2 inhibitors RO5353 and RO2468 for potential clinical development. ACS Med. Chem. Lett., 2014, 5(2), 124-127.
[http://dx.doi.org/10.1021/ml400359z] [PMID: 24900784]
[76]
Arnhold, V.; Schmelz, K.; Proba, J.; Winkler, A.; Wünschel, J.; Toedling, J.; Deubzer, H.E.; Künkele, A.; Eggert, A.; Schulte, J.H.; Hundsdoerfer, P. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma. Oncotarget, 2018, 9(2), 2304-2319.
[http://dx.doi.org/10.18632/oncotarget.23409] [PMID: 29416773]
[77]
Ding, Q.; Zhang, Z.; Liu, J.J.; Jiang, N.; Zhang, J.; Ross, T.M.; Chu, X.J.; Bartkovitz, D.; Podlaski, F.; Janson, C.; Tovar, C.; Filipovic, Z.M.; Higgins, B.; Glenn, K.; Packman, K.; Vassilev, L.T.; Graves, B. Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development. J. Med. Chem., 2013, 56(14), 5979-5983.
[http://dx.doi.org/10.1021/jm400487c] [PMID: 23808545]
[78]
Zhou, Z.; Zalutsky, M.R.; Chitneni, S.K. Fluorine-18 labeling of the MDM2 inhibitor RG7388 for PET imaging: Chemistry and preliminary evaluation. Mol. Pharm., 2021, 18(10), 3871-3881.
[http://dx.doi.org/10.1021/acs.molpharmaceut.1c00531] [PMID: 34523337]
[79]
Vu, B.; Wovkulich, P.; Pizzolato, G.; Lovey, A.; Ding, Q.; Jiang, N.; Liu, J.J.; Zhao, C.; Glenn, K.; Wen, Y.; Tovar, C.; Packman, K.; Vassilev, L.; Graves, B. Discovery of RG7112: A small-molecule MDM2 inhibitor in clinical development. ACS Med. Chem. Lett., 2013, 4(5), 466-469.
[http://dx.doi.org/10.1021/ml4000657] [PMID: 24900694]
[80]
He, S.; Dong, G.; Wu, S.; Fang, K.; Miao, Z.; Wang, W.; Sheng, C. Small molecules simultaneously inhibiting p53-murine double minute 2 (MDM2) interaction and histone deacetylases (HDACs): Discovery of novel multitargeting antitumor agents. J. Med. Chem., 2018, 61(16), 7245-7260.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00664] [PMID: 30045621]
[81]
Dong, G.; He, S.; Qin, X.; Liu, T.; Jiang, Y.; Li, X.; Chen, L.; Han, G.; Sheng, C.; Li, M. Discovery of nonpeptide, environmentally sensitive fluorescent probes for imaging p53-MDM2 interactions in living cell lines and tissue slice. Anal. Chem., 2020, 92(3), 2642-2648.
[http://dx.doi.org/10.1021/acs.analchem.9b04551] [PMID: 31918545]
[82]
Zhuang, C.; Miao, Z.; Wu, Y.; Guo, Z.; Li, J.; Yao, J.; Xing, C.; Sheng, C.; Zhang, W. Double-edged swords as cancer therapeutics: Novel, orally active, small molecules simultaneously inhibit p53-MDM2 interaction and the NF-κB pathway. J. Med. Chem., 2014, 57(3), 567-577.
[http://dx.doi.org/10.1021/jm401800k] [PMID: 24428757]
[83]
Zhuang, C.; Miao, Z.; Zhu, L.; Dong, G.; Guo, Z.; Wang, S.; Zhang, Y.; Wu, Y.; Yao, J.; Sheng, C.; Zhang, W. Discovery, synthesis, and biological evaluation of orally active pyrrolidone derivatives as novel inhibitors of p53-MDM2 protein-protein interaction. J. Med. Chem., 2012, 55(22), 9630-9642.
[http://dx.doi.org/10.1021/jm300969t] [PMID: 23046248]
[84]
Konopleva, M.; Martinelli, G.; Daver, N.; Papayannidis, C.; Wei, A.; Higgins, B.; Ott, M.; Mascarenhas, J.; Andreeff, M. MDM2 inhibition: An important step forward in cancer therapy. Leukemia, 2020, 34(11), 2858-2874.
[http://dx.doi.org/10.1038/s41375-020-0949-z] [PMID: 32651541]
[85]
Rew, Y.; Sun, D.; Gonzalez-Lopez De Turiso, F.; Bartberger, M.D.; Beck, H.P.; Canon, J.; Chen, A.; Chow, D.; Deignan, J.; Fox, B.M.; Gustin, D.; Huang, X.; Jiang, M.; Jiao, X.; Jin, L.; Kayser, F.; Kopecky, D.J.; Li, Y.; Lo, M.C.; Long, A.M.; Michelsen, K.; Oliner, J.D.; Osgood, T.; Ragains, M.; Saiki, A.Y.; Schneider, S.; Toteva, M.; Yakowec, P.; Yan, X.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Medina, J.C.; Olson, S.H. Structure-based design of novel inhibitors of the MDM2-p53 interaction. J. Med. Chem., 2012, 55(11), 4936-4954.
[http://dx.doi.org/10.1021/jm300354j] [PMID: 22524527]
[86]
Rew, Y.; Sun, D. Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer. J. Med. Chem., 2014, 57(15), 6332-6341.
[http://dx.doi.org/10.1021/jm500627s] [PMID: 24967612]
[87]
Gonzalez, A.Z.; Li, Z.; Beck, H.P.; Canon, J.; Chen, A.; Chow, D.; Duquette, J.; Eksterowicz, J.; Fox, B.M.; Fu, J.; Huang, X.; Houze, J.; Jin, L.; Li, Y.; Ling, Y.; Lo, M.C.; Long, A.M.; McGee, L.R.; McIntosh, J.; Oliner, J.D.; Osgood, T.; Rew, Y.; Saiki, A.Y.; Shaffer, P.; Wortman, S.; Yakowec, P.; Yan, X.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Olson, S.H.; Sun, D.; Medina, J.C. Novel inhibitors of the MDM2-p53 interaction featuring hydrogen bond acceptors as carboxylic acid isosteres. J. Med. Chem., 2014, 57(7), 2963-2988.
[http://dx.doi.org/10.1021/jm401911v] [PMID: 24601644]
[88]
Yu, M.; Wang, Y.; Zhu, J.; Bartberger, M.D.; Canon, J.; Chen, A.; Chow, D.; Eksterowicz, J.; Fox, B.; Fu, J.; Gribble, M.; Huang, X.; Li, Z.; Liu, J.J.; Lo, M.; McMinn, D.; Oliner, J.D.; Osgood, T.; Rew, Y.; Saiki, A.Y.; Shaffer, P.; Yan, X.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Olson, S.H.; Medina, J.C.; Sun, D. Discovery of potent and simplified piperidinone-based inhibitors of the MDM2–p53 interaction. ACS Med. Chem. Lett., 2014, 5(8), 894-899.
[http://dx.doi.org/10.1021/ml500142b] [PMID: 25147610]
[89]
Gonzalez, A.Z.; Eksterowicz, J.; Bartberger, M.D.; Beck, H.P.; Canon, J.; Chen, A.; Chow, D.; Duquette, J.; Fox, B.M.; Fu, J.; Huang, X.; Houze, J.B.; Jin, L.; Li, Y.; Li, Z.; Ling, Y.; Lo, M.C.; Long, A.M.; McGee, L.R.; McIntosh, J.; McMinn, D.L.; Oliner, J.D.; Osgood, T.; Rew, Y.; Saiki, A.Y.; Shaffer, P.; Wortman, S.; Yakowec, P.; Yan, X.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Olson, S.H.; Medina, J.C.; Sun, D. Selective and potent morpholinone inhibitors of the MDM2-p53 protein-protein interaction. J. Med. Chem., 2014, 57(6), 2472-2488.
[http://dx.doi.org/10.1021/jm401767k] [PMID: 24548297]
[90]
Rew, Y.; Sun, D.; Yan, X.; Beck, H.P.; Canon, J.; Chen, A.; Duquette, J.; Eksterowicz, J.; Fox, B.M.; Fu, J.; Gonzalez, A.Z.; Houze, J.; Huang, X.; Jiang, M.; Jin, L.; Li, Y.; Li, Z.; Ling, Y.; Lo, M.C.; Long, A.M.; McGee, L.R.; McIntosh, J.; Oliner, J.D.; Osgood, T.; Saiki, A.Y.; Shaffer, P.; Wang, Y.C.; Wortman, S.; Yakowec, P.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Medina, J.C.; Olson, S.H. Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the MDM2-p53 interaction. J. Med. Chem., 2014, 57(24), 10499-10511.
[http://dx.doi.org/10.1021/jm501550p] [PMID: 25384157]
[91]
Gessier, F.; Kallen, J.; Jacoby, E.; Chène, P.; Stachyra-Valat, T.; Ruetz, S.; Jeay, S.; Holzer, P.; Masuya, K.; Furet, P. Discovery of dihydroisoquinolinone derivatives as novel inhibitors of the p53–MDM2 interaction with a distinct binding mode. Bioorg. Med. Chem. Lett., 2015, 25(17), 3621-3625.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.058] [PMID: 26141769]
[92]
Bogen, S.L.; Pan, W.; Gibeau, C.R.; Lahue, B.R.; Ma, Y.; Nair, L.G.; Seigel, E.; Shipps, G.W., Jr; Tian, Y.; Wang, Y.; Lin, Y.; Liu, M.; Liu, S.; Mirza, A.; Wang, X.; Lipari, P.; Seidel-Dugan, C.; Hicklin, D.J.; Bishop, W.R.; Rindgen, D.; Nomeir, A.; Prosise, W.; Reichert, P.; Scapin, G.; Strickland, C.; Doll, R.J. Discovery of novel 3, 3-disubstituted piperidines as orally bioavailable, potent, and efficacious HDM2-p53 inhibitors. ACS Med. Chem. Lett., 2016, 7(3), 324-329.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00472] [PMID: 26985323]
[93]
Holzer, P.; Masuya, K.; Furet, P.; Kallen, J.; Valat-Stachyra, T.; Ferretti, S.; Berghausen, J.; Bouisset-Leonard, M.; Buschmann, N.; Pissot-Soldermann, C.; Rynn, C.; Ruetz, S.; Stutz, S.; Chène, P.; Jeay, S.; Gessier, F. Discovery of a dihydroisoquinolinone derivative (NVP-CGM097): a highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumors. J. Med. Chem., 2015, 58(16), 6348-6358.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00810] [PMID: 26181851]
[94]
Wang, W.; Qin, J.J.; Voruganti, S.; Srivenugopal, K.S.; Nag, S.; Patil, S.; Sharma, H.; Wang, M.H.; Wang, H.; Buolamwini, J.K.; Zhang, R. The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models. Nat. Commun., 2014, 5(1), 5086.
[http://dx.doi.org/10.1038/ncomms6086] [PMID: 25271708]
[95]
Chauhan, S.S.; Singh, A.K.; Meena, S.; Lohani, M.; Singh, A.; Arya, R.K.; Cheruvu, S.H.; Sarkar, J.; Gayen, J.R.; Datta, D.; Chauhan, P.M.S. Synthesis of novel β-carboline based chalcones with high cytotoxic activity against breast cancer cells. Bioorg. Med. Chem. Lett., 2014, 24(13), 2820-2824.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.109] [PMID: 24844196]
[96]
Zheng, G.; Shen, J.; Zhan, Y.; Yi, H.; Xue, S.; Wang, Z.; Ji, X.; Li, Z. Design, synthesis and in vitro and in vivo antitumour activity of 3-benzylideneindolin-2-one derivatives, a novel class of small-molecule inhibitors of the MDM2–p53 interaction. Eur. J. Med. Chem., 2014, 81, 277-288.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.027] [PMID: 24852275]
[97]
Daniele, S.; La Pietra, V.; Barresi, E.; Di Maro, S.; Da Pozzo, E.; Robello, M.; La Motta, C.; Cosconati, S.; Taliani, S.; Marinelli, L.; Novellino, E.; Martini, C.; Da Settimo, F. Lead optimization of 2-phenylindolylglyoxylyldipeptide murine double minute (MDM) 2/translocator protein (TSPO) dual inhibitors for the treatment of gliomas. J. Med. Chem., 2016, 59(10), 4526-4538.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01767] [PMID: 27050782]
[98]
Surmiak, E.; Twarda-Clapa, A.; Zak, K.M.; Musielak, B.; Tomala, M.D.; Kubica, K.; Grudnik, P.; Madej, M.; Jablonski, M.; Potempa, J.; Kalinowska-Tluscik, J.; Dömling, A.; Dubin, G.; Holak, T.A. A unique MDM2-binding mode of the 3-pyrrolin-2-one-and 2-furanone-based antagonists of the p53-MDM2 interaction. ACS Chem. Biol., 2016, 11(12), 3310-3318.
[http://dx.doi.org/10.1021/acschembio.6b00596] [PMID: 27709883]
[99]
Sang, P.; Shi, Y.; Lu, J.; Chen, L.; Yang, L.; Borcherds, W.; Abdulkadir, S.; Li, Q.; Daughdrill, G.; Chen, J.; Cai, J. α-Helix-mimicking sulfono-γ-AApeptide inhibitors for p53–MDM2/MDMX protein–protein interactions. J. Med. Chem., 2020, 63(3), 975-986.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00993] [PMID: 31971801]
[100]
Chessari, G.; Hardcastle, I.R.; Ahn, J.S.; Anil, B.; Anscombe, E.; Bawn, R.H.; Bevan, L.D.; Blackburn, T.J.; Buck, I.; Cano, C.; Carbain, B.; Castro, J.; Cons, B.; Cully, S.J.; Endicott, J.A.; Fazal, L.; Golding, B.T.; Griffin, R.J.; Haggerty, K.; Harnor, S.J.; Hearn, K.; Hobson, S.; Holvey, R.S.; Howard, S.; Jennings, C.E.; Johnson, C.N.; Lunec, J.; Miller, D.C.; Newell, D.R.; Noble, M.E.M.; Reeks, J.; Revill, C.H.; Riedinger, C.; St Denis, J.D.; Tamanini, E.; Thomas, H.; Thompson, N.T.; Vinković, M.; Wedge, S.R.; Williams, P.A.; Wilsher, N.E.; Zhang, B.; Zhao, Y. Structure-based design of potent and orally active isoindolinone inhibitors of MDM2-p53 protein-protein interaction. J. Med. Chem., 2021, 64(7), 4071-4088.
[http://dx.doi.org/10.1021/acs.jmedchem.0c02188] [PMID: 33761253]
[101]
Gicquel, M.; Gomez, C.; Garcia Alvarez, M.C.; Pamlard, O.; Guérineau, V.; Jacquet, E.; Bignon, J.; Voituriez, A.; Marinetti, A. Inhibition of p53-murine double minute 2 (MDM2) interactions with 3, 3′-spirocyclopentene oxindole derivatives. J. Med. Chem., 2018, 61(20), 9386-9392.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01137] [PMID: 30221935]
[102]
Wang, S.; Jiang, Y.; Wu, S.; Dong, G.; Miao, Z.; Zhang, W.; Sheng, C. Meeting organocatalysis with drug discovery: asymmetric synthesis of 3, 3′-Spirooxindoles fused with tetrahydrothiopyrans as novel p53-MDM2 inhibitors. Org. Lett., 2016, 18(5), 1028-1031.
[http://dx.doi.org/10.1021/acs.orglett.6b00155] [PMID: 26883465]
[103]
Ribeiro, C.J.A.; Amaral, J.D.; Rodrigues, C.M.P.; Moreira, R.; Santos, M.M.M. Spirooxadiazoline oxindoles with promising in vitro antitumor activities. MedChemComm, 2016, 7(3), 420-425.
[http://dx.doi.org/10.1039/C5MD00450K]
[104]
Giofrè, S.V.; Cirmi, S.; Mancuso, R.; Nicolò, F.; Lanza, G.; Legnani, L.; Campisi, A.; Chiacchio, M.A.; Navarra, M.; Gabriele, B.; Romeo, R. Synthesis of spiro[isoindole-1,5′-isoxazolidin]-3(2 H )-ones as potential inhibitors of the MDM2-p53 interaction. Beilstein J. Org. Chem., 2016, 12(1), 2793-2807.
[http://dx.doi.org/10.3762/bjoc.12.278] [PMID: 28144352]
[105]
Zhao, Y.; Yu, S.; Sun, W.; Liu, L.; Lu, J.; McEachern, D.; Shargary, S.; Bernard, D.; Li, X.; Zhao, T.; Zou, P.; Sun, D.; Wang, S. A potent small-molecule inhibitor of the MDM2-p53 interaction (MI-888) achieved complete and durable tumor regression in mice. J. Med. Chem., 2013, 56(13), 5553-5561.
[http://dx.doi.org/10.1021/jm4005708] [PMID: 23786219]
[106]
Wang, S.; Sun, W.; Zhao, Y.; McEachern, D.; Meaux, I.; Barrière, C.; Stuckey, J.A.; Meagher, J.L.; Bai, L.; Liu, L.; Hoffman-Luca, C.G.; Lu, J.; Shangary, S.; Yu, S.; Bernard, D.; Aguilar, A.; Dos-Santos, O.; Besret, L.; Guerif, S.; Pannier, P.; Gorge-Bernat, D.; Debussche, L. SAR405838: An optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression. Cancer Res., 2014, 74(20), 5855-5865.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0799] [PMID: 25145672]
[107]
Aguilar, A.; Sun, W.; Liu, L.; Lu, J.; McEachern, D.; Bernard, D.; Deschamps, J.R.; Wang, S. Design of chemically stable, potent, and efficacious MDM2 inhibitors that exploit the retro-mannich ring-opening-cyclization reaction mechanism in spiro-oxindoles. J. Med. Chem., 2014, 57(24), 10486-10498.
[http://dx.doi.org/10.1021/jm501541j] [PMID: 25496041]
[108]
Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Wang, G.; Qiu, S.; Shangary, S.; Gao, W.; Qin, D.; Stuckey, J.; Krajewski, K.; Roller, P.P.; Wang, S. Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J. Med. Chem., 2006, 49(12), 3432-3435.
[http://dx.doi.org/10.1021/jm051122a] [PMID: 16759082]
[109]
Gollner, A.; Rudolph, D.; Arnhof, H.; Bauer, M.; Blake, S.M.; Boehmelt, G.; Cockroft, X.L.; Dahmann, G.; Ettmayer, P.; Gerstberger, T.; Karolyi-Oezguer, J.; Kessler, D.; Kofink, C.; Ramharter, J.; Rinnenthal, J.; Savchenko, A.; Schnitzer, R.; Weinstabl, H.; Weyer-Czernilofsky, U.; Wunberg, T.; McConnell, D.B. Discovery of novel spiro [3 H-indole-3, 2′-pyrrolidin]-2 (1 H)-one compounds as chemically stable and orally active inhibitors of the MDM2–p53 interaction. J. Med. Chem., 2016, 59(22), 10147-10162.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00900] [PMID: 27775892]
[110]
Yang, M.C.; Peng, C.; Huang, H.; Yang, L.; He, X.H.; Huang, W.; Cui, H.L.; He, G.; Han, B. Organocatalytic asymmetric synthesis of spiro-oxindole piperidine derivatives that reduce cancer cell proliferation by inhibiting MDM2–p53 interaction. Org. Lett., 2017, 19(24), 6752-6755.
[http://dx.doi.org/10.1021/acs.orglett.7b03516] [PMID: 29210587]
[111]
Soares, J.; Espadinha, M.; Raimundo, L.; Ramos, H.; Gomes, A.S.; Gomes, S.; Loureiro, J.B.; Inga, A.; Reis, F.; Gomes, C.; Santos, M.M.M.; Saraiva, L. DIMP53-1: A novel small-molecule dual inhibitor of p53-MDM2/X interactions with multifunctional p53-dependent anticancer properties. Mol. Oncol., 2017, 11(6), 612-627.
[http://dx.doi.org/10.1002/1878-0261.12051] [PMID: 28296148]
[112]
Wurz, R.P.; Cee, V.J. Targeted degradation of MDM2 as a new approach to improve the efficacy of MDM2-p53 inhibitors. J. Med. Chem., 2019, 62(2), 445-447.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01945] [PMID: 30575392]
[113]
Li, Y.; Yang, J.; Aguilar, A.; McEachern, D.; Przybranowski, S.; Liu, L.; Yang, C.Y.; Wang, M.; Han, X.; Wang, S. 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. J. Med. Chem., 2019, 62(2), 448-466.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00909] [PMID: 30525597]
[114]
Miyazaki, M.; Naito, H.; Sugimoto, Y.; Kawato, H.; Okayama, T.; Shimizu, H.; Miyazaki, M.; Kitagawa, M.; Seki, T.; Fukutake, S.; Aonuma, M.; Soga, T. Lead optimization of novel p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Bioorg. Med. Chem. Lett., 2013, 23(3), 728-732.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.091] [PMID: 23266121]
[115]
Miyazaki, M.; Uoto, K.; Sugimoto, Y.; Naito, H.; Yoshida, K.; Okayama, T.; Kawato, H.; Miyazaki, M.; Kitagawa, M.; Seki, T.; Fukutake, S.; Aonuma, M.; Soga, T. Discovery of DS-5272 as a promising candidate: A potent and orally active p53–MDM2 interaction inhibitor. Bioorg. Med. Chem., 2015, 23(10), 2360-2367.
[http://dx.doi.org/10.1016/j.bmc.2015.03.069] [PMID: 25882531]
[116]
Twarda-Clapa, A.; Krzanik, S.; Kubica, K.; Guzik, K.; Labuzek, B.; Neochoritis, C.G.; Khoury, K.; Kowalska, K.; Czub, M.; Dubin, G.; Dömling, A.; Skalniak, L.; Holak, T.A. 1, 4, 5-trisubstituted imidazole-based p53–MDM2/MDMX antagonists with aliphatic linkers for conjugation with biological carriers. J. Med. Chem., 2017, 60(10), 4234-4244.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00104] [PMID: 28482147]
[117]
Guo, Z.; Zhuang, C.; Zhu, L.; Zhang, Y.; Yao, J.; Dong, G.; Wang, S.; Liu, Y.; Chen, H.; Sheng, C.; Miao, Z.; Zhang, W. Structure–activity relationship and antitumor activity of thio-benzodiazepines as p53–MDM2 protein–protein interaction inhibitors. Eur. J. Med. Chem., 2012, 56, 10-16.
[http://dx.doi.org/10.1016/j.ejmech.2012.08.003] [PMID: 22940704]
[118]
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.; Julian, L.D.; Kayser, F.; Lo, M.C.; Long, A.M.; McMinn, D.; Oliner, J.D.; Osgood, T.; Powers, J.P.; Saiki, A.Y.; Schneider, S.; Shaffer, P.; Xiao, S.H.; Yakowec, P.; Yan, X.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Medina, J.C.; Olson, S.H. Rational design and binding mode duality of MDM2-p53 inhibitors. J. Med. Chem., 2013, 56(10), 4053-4070.
[http://dx.doi.org/10.1021/jm400293z] [PMID: 23597064]
[119]
Xue, X.; Wei, J.L.; Xu, L.L.; Xi, M.Y.; Xu, X.L.; Liu, F.; Guo, X.K.; Wang, L.; Zhang, X.J.; Zhang, M.Y.; Lu, M.C.; Sun, H.P.; You, Q.D. Effective screening strategy using ensembled pharmacophore models combined with cascade docking: application to p53-MDM2 interaction inhibitors. J. Chem. Inf. Model., 2013, 53(10), 2715-2729.
[http://dx.doi.org/10.1021/ci400348f] [PMID: 24050442]
[120]
Yu, Z.; Zhuang, C.; Wu, Y.; Guo, Z.; Li, J.; Dong, G.; Yao, J.; Sheng, C.; Miao, Z.; Zhang, W. Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors. Int. J. Mol. Sci., 2014, 15(9), 15741-15753.
[http://dx.doi.org/10.3390/ijms150915741] [PMID: 25198897]
[121]
Pereira, D.; Lima, R.T.; Palmeira, A.; Seca, H.; Soares, J.; Gomes, S.; Raimundo, L.; Maciel, C.; Pinto, M.; Sousa, E.; Helena Vasconcelos, M.; Saraiva, L.; Cidade, H. Design and synthesis of new inhibitors of p53–MDM2 interaction with a chalcone scaffold. Arab. J. Chem., 2019, 12(8), 4150-4161.
[http://dx.doi.org/10.1016/j.arabjc.2016.04.015]
[122]
Chen, S.; Li, X.; Yuan, W.; Zou, Y.; Guo, Z.; Chai, Y.; Lu, W. Rapid identification of dual p53-MDM2/MDMX interaction inhibitors through virtual screening and hit based substructure search. RSC Advances, 2017, 7(16), 9989-9997.
[http://dx.doi.org/10.1039/C7RA00473G]
[123]
Shankar, S.; Faheem, M.M.; Nayak, D.; Wani, N.A.; Farooq, S.; Koul, S.; Goswami, A.; Rai, R. Cyclodipeptide c (orn-pro) conjugate with 4-ethylpiperic acid abrogates cancer cell metastasis through modulating mdm2. Bioconjug. Chem., 2018, 29(1), 164-175.
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00670] [PMID: 29216716]
[124]
Oliveira Ribeiro, H.; Cortez, A.P.; Ávila, R.I.; Silva, A.C.G.; Carvalho, F.S.; Menegatti, R.; Lião, L.M.; Valadares, M.C. Small-molecule MDM2 inhibitor LQFM030-induced apoptosis in p53-null K562 chronic myeloid leukemia cells. Fundam. Clin. Pharmacol., 2020, 34(4), 444-457.
[http://dx.doi.org/10.1111/fcp.12540] [PMID: 32011031]
[125]
Wang, Z.; Zhan, Y.; Xu, J.; Wang, Y.; Sun, M.; Chen, J.; Liang, T.; Wu, L.; Xu, K. β-sitosterol reverses multidrug resistance via BCRP suppression by inhibiting the p53–MDM2 interaction in colorectal cancer. J. Agric. Food Chem., 2020, 68(12), 3850-3858.
[http://dx.doi.org/10.1021/acs.jafc.0c00107] [PMID: 32167760]
[126]
Wu, Z.; Gu, L.; Zhang, S.; Liu, T.; Lukka, P.B.; Meibohm, B.; Bollinger, J.C.; Zhou, M.; Li, W. Discovery of N -(3,4-Dimethylphenyl)-4-(4-isobutyrylphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2- c ]quinoline-8-sulfonamide as a potent dual MDM2/XIAP inhibitor. J. Med. Chem., 2021, 64(4), 1930-1950.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00932] [PMID: 33556244]
[127]
Chessari, G.; Howard, S.; Buck, I. M.; Cons, B. D.; Johnson, C. N.; Holvey, R. S.; Rees, D. C. Isoindolinone inhibitors of the MDM2-P53 interaction having anticancer activity. Patent US10, 526, 311 B2, 2020.
[128]
Chessari, G.; Howard, S.; Buck, I. M.; Cons, B. D.; Johnson, C. N.; Holvey, R. S.; Rees, D. C. Isoindolinone inhibitors of the MDM2-p53 interaction having anticancer activity. Patent US10, 981, 898 B2, 2021.
[129]
Ramharter, J.; Broeker, J.; Gille, A.; Gollner, A.; Henry, M.; Kerres, N.; Weinstabl, H. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-p53 inhibitors. Patent US10, 246, 467 B2, 2019.
[130]
Gollner, A.; Broeker, J.; Kerres, N.; Kofink, C.; Ramharter, J.; Weinstabl, H. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-P53 inhibitors. Patent US10, 144, 739 B2, 2018.
[131]
Gollner, A.; Broeker, J.; Kerres, N.; Kofink, C.; Ramharter, J.; Weinstabl, H.; Gille, A.; Goepper, S.; Henry, M.; Huchler, G. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-P53 inhibitors. Patent US10, 882, 866 B1, 2021.
[132]
Chessari, G.; Howard, S.; Buck, I. M.; Cons, B. D.; Johnson, C. N.; Holvey, R. S.; Rees, D. C. Isoindolinone inhibitors of the MDM2-p53 interaction having anticancer activity. Patent US10, 544, 132 B2, 2020.
[133]
Gollner, A.; Broeker, J.; Kerres, N.; Kofink, C.; Ramharter, J.; Weinstabl, H.; Gille, A.; Goepper, S.; Henry, M.; Huchler, G. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-P53 inhibitors. Patent US10, 717, 742 B2, 2020.
[134]
Chen, Y.; Ding, Q. J.; Sun, Y.-S. Spiropyrrolidines as MDM2 inhibitors. Patent US9, 701, 685 B2, 2017.
[135]
Weinstabl, H.; Gollner, A.; Ramharter, J.; Wunberg, T. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-P53 inhibitors. Patent US 10, 576, 064 B2, 2020.
[136]
Gollner, A.; Kofink, C.; Ramharter, J.; Weinstabl, H.; Wunberg, T. Spiro [3H-indole-3, 2′-pyrrolidin]-2 (1H)-one compounds and derivatives as MDM2-P53 inhibitors. Patent US 10 ,138,251 B2, 2018.
[137]
Ramharter, J.; Broeker, J.; Gille, A.; Gollner, A.; Henry, M. New spiro [3h-indole-3, 2´-pyrrolidin]-2 (1h)-one compounds and derivatives as mdm2-p53 inhibitors. Patent EP 3 183 254 B1, 2019.
[138]
Arora, P. S.; Lao, B. B.; Guarracino, D.; Bonneau, R.; Drew, K. Oxopiperazine helix mimetics as inhibitors of the p53-MDM2 interaction. Patent US 11,180,481 B2, 2021.
[139]
Zhang, R.; Wang, W. Cancer treatment utilizing SP-141 to bind with MDM2 and act as an inhibitor of MDM2 expression. Patent US 10,472,355 B2, 2019.

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