{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:14:24Z","timestamp":1772572464955,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T00:00:00Z","timestamp":1565395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Half of human cancers harbor TP53 mutations that render p53 inactive as a tumor suppressor. In these cancers, reactivation of mutant p53 (mutp53) through restoration of wild-type-like function constitutes a valuable anticancer therapeutic strategy. In order to search for mutp53 reactivators, a small library of tryptophanol-derived oxazoloisoindolinones was synthesized and the potential of these compounds as mutp53 reactivators and anticancer agents was investigated in human tumor cells and xenograft mouse models. By analysis of their anti-proliferative effect on a panel of p53-null NCI-H1299 tumor cells ectopically expressing highly prevalent mutp53, the compound SLMP53-2 was selected based on its potential reactivation of multiple structural mutp53. In mutp53-Y220C-expressing hepatocellular carcinoma (HCC) cells, SLMP53-2-induced growth inhibition was mediated by cell cycle arrest, apoptosis, and endoplasmic reticulum stress response. In these cells, SLMP53-2 restored wild-type-like conformation and DNA-binding ability of mutp53-Y220C by enhancing its interaction with the heat shock protein 70 (Hsp70), leading to the reestablishment of p53 transcriptional activity. Additionally, SLMP53-2 displayed synergistic effect with sorafenib, the only approved therapy for advanced HCC. Notably, it exhibited potent antitumor activity in human HCC xenograft mouse models with a favorable toxicological profile. Collectively, SLMP53-2 is a new mutp53-targeting agent with promising antitumor activity, particularly against HCC.<\/jats:p>","DOI":"10.3390\/cancers11081151","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T06:38:02Z","timestamp":1565591882000},"page":"1151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["SLMP53-2 Restores Wild-Type-Like Function to Mutant p53 through Hsp70: Promising Activity in Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Sara","family":"Gomes","sequence":"first","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Bartolomeo","family":"Bosco","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy"}]},{"given":"Joana B.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-9998","authenticated-orcid":false,"given":"Helena","family":"Ramos","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-2601","authenticated-orcid":false,"given":"Liliana","family":"Raimundo","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Joana","family":"Soares","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Nair","family":"Nazareth","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Valentina","family":"Barcherini","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-7627","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Domingues","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Alessandra","family":"Bisio","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7156-5434","authenticated-orcid":false,"given":"Silvano","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-6483","authenticated-orcid":false,"given":"Matthias R.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1867-0486","authenticated-orcid":false,"given":"Jo\u00e3o P.","family":"Br\u00e1s","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Institute of Biomedical Engineering, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-8587","authenticated-orcid":false,"given":"Maria In\u00eas","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Institute of Biomedical Engineering, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"C\u00e9lia","family":"Gomes","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, CNC.IBILI Consortium &amp; CIBB Consortium, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9554","authenticated-orcid":false,"given":"Fl\u00e1vio","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology &amp; Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, CNC.IBILI Consortium &amp; CIBB Consortium, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Alan R.","family":"Fersht","sequence":"additional","affiliation":[{"name":"Medical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-1637","authenticated-orcid":false,"given":"Alberto","family":"Inga","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, 38123 Trento, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-9353","authenticated-orcid":false,"given":"Maria M. M.","family":"Santos","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Biological Sciences, Laboratory of Microbiology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2017.08.028","article-title":"Putting p53 in Context","volume":"170","author":"Kastenhuber","year":"2017","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Schulz-Heddergott, R., and Moll, U.M. (2018). Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target. Cancers, 10.","DOI":"10.3390\/cancers10060188"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1038\/sj.onc.1210291","article-title":"Structure-function-rescue: The diverse nature of common p53 cancer mutants","volume":"26","author":"Joerger","year":"2007","journal-title":"Oncogene"},{"key":"ref_4","unstructured":"Lopes, E.A., Gomes, S., Saraiva, L., and Santos, M. (2018). Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment. Curr. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrc.2017.109","article-title":"Targeting mutant p53 for efficient cancer therapy","volume":"18","author":"Bykov","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2018). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.fr\/today."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cld.2015.01.012","article-title":"Nonalcoholic Fatty liver disease, diabetes, obesity, and hepatocellular carcinoma","volume":"19","author":"Noureddin","year":"2015","journal-title":"Clin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"iv238","DOI":"10.1093\/annonc\/mdy308","article-title":"Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Vogel","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1159\/000343828","article-title":"Treatment of hepatocellular carcinoma: A systematic review","volume":"1","author":"Lin","year":"2012","journal-title":"Liver Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"404","DOI":"10.21037\/hbsn.2017.10.02","article-title":"Landscape of genomic alterations in hepatocellular carcinoma: Current knowledge and perspectives for targeted therapies","volume":"6","author":"Bevant","year":"2017","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_11","unstructured":"(2017). Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma. Cell, 169, 1327\u20131341."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4326","DOI":"10.18632\/oncotarget.6775","article-title":"Reactivation of wild-type and mutant p53 by tryptophanolderived oxazoloisoindolinone SLMP53-1, a novel anticancer small-molecule","volume":"7","author":"Soares","year":"2016","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10360","DOI":"10.1073\/pnas.0805326105","article-title":"Targeted rescue of a destabilized mutant of p53 by an in silico screened drug","volume":"105","author":"Boeckler","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1111\/cas.13792","article-title":"Tumor suppressive role for kinases phosphorylating p53 in DNA damage-induced apoptosis","volume":"109","author":"Yogosawa","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6203","DOI":"10.1158\/1078-0432.CCR-17-0098","article-title":"BRAF Inhibitors Amplify the Proapoptotic Activity of MEK Inhibitors by Inducing ER Stress in NRAS-Mutant Melanoma","volume":"23","author":"Niessner","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.molcel.2007.05.017","article-title":"Transcriptional activation of miR-34a contributes to p53-mediated apoptosis","volume":"26","author":"Marciano","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/sj.cdd.4402022","article-title":"Hypoxia induces p53-dependent transactivation and Fas\/CD95-dependent apoptosis","volume":"14","author":"Liu","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/sj.emboj.7600596","article-title":"TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death","volume":"24","author":"Ohoka","year":"2005","journal-title":"EMBO J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nrm2395","article-title":"Transcriptional control of human p53-regulated genes","volume":"9","author":"Riley","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1038\/sj.onc.1202041","article-title":"Human tumor-derived p53 proteins exhibit binding site selectivity and temperature sensitivity for transactivation in a yeast-based assay","volume":"16","author":"Prives","year":"1998","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3513","DOI":"10.1002\/j.1460-2075.1992.tb05434.x","article-title":"Interaction of heat-shock protein 70 with p53 translated in vitro: Evidence for interaction with dimeric p53 and for a role in the regulation of p53 conformation","volume":"11","author":"Hainaut","year":"1992","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1038\/onc.2009.281","article-title":"Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions","volume":"28","author":"Walerych","year":"2009","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbcan.2017.12.004","article-title":"Chaperoning the guardian of the genome. The two-faced role of molecular chaperones in p53 tumor suppressor action","volume":"1869","author":"Wawrzynow","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_24","unstructured":"Giknis, M., and Clifford, C.B. (2008). Clinical Laboratory Parameters for CRL: WI (Han), Charles River Laboratories."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/nrd2755","article-title":"Cell death and endoplasmic reticulum stress: Disease relevance and therapeutic opportunities","volume":"7","author":"Kim","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of oxidative stress as an anticancer strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/bjc.2016.72","article-title":"Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: Results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours","volume":"114","author":"Mahalingam","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1038\/srep03219","article-title":"Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress","volume":"3","author":"Yang","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E5271","DOI":"10.1073\/pnas.1610421113","article-title":"2-Sulfonylpyrimidines: Mild alkylating agents with anticancer activity toward p53-compromised cells","volume":"113","author":"Bauer","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/onc.2009.425","article-title":"Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis","volume":"29","author":"Lambert","year":"2010","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Liu, J.L., Zhang, X.J., Zhang, Z., Zhang, A.H., Wang, W., and Dong, J.H. (2013). Meta-analysis: Prognostic value of survivin in patients with hepatocellular carcinoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083350"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9905","DOI":"10.1007\/s13277-014-2279-0","article-title":"The expression of Survivin and NF-kappaB associated with prognostically worse clinicopathologic variables in hepatocellular carcinoma","volume":"35","author":"Jin","year":"2014","journal-title":"Tumour Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.canlet.2015.06.016","article-title":"Survivin in survival of hepatocellular carcinoma","volume":"379","author":"Su","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e3100","DOI":"10.1038\/cddis.2017.495","article-title":"Alternative mechanisms of miR-34a regulation in cancer","volume":"8","author":"Slabakova","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.canlet.2008.09.035","article-title":"miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells","volume":"275","author":"Li","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1158\/1535-7163.MCT-14-0209","article-title":"Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer","volume":"13","author":"Daige","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s10637-016-0407-y","article-title":"Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors","volume":"35","author":"Beg","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.chembiol.2015.07.016","article-title":"Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis","volume":"22","author":"Hiraki","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.canlet.2019.03.047","article-title":"Mutant p53(R175H) promotes cancer initiation in the pancreas by stabilizing HSP70","volume":"453","author":"Polireddy","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1080\/14656566.2017.1378346","article-title":"An in-depth review of chemical angiogenesis inhibitors for treating hepatocellular carcinoma","volume":"18","author":"Raoul","year":"2017","journal-title":"Expert Opin. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000481244","article-title":"Systemic Therapy for Hepatocellular Carcinoma: 2017 Update","volume":"93","author":"Kudo","year":"2017","journal-title":"Oncology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1002\/cmdc.201500429","article-title":"Enantiopure Indolizinoindolones with in vitro Activity against Blood- and Liver-Stage Malaria Parasites","volume":"10","author":"Pereira","year":"2015","journal-title":"Chem. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ejmech.2018.04.035","article-title":"Aminobenzothiazole derivatives stabilize the thermolabile p53 cancer mutant Y220C and show anticancer activity in p53-Y220C cell lines","volume":"152","author":"Baud","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.canlet.2019.01.014","article-title":"New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma","volume":"446","author":"Gomes","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2015.03.006","article-title":"A tryptophanol-derived oxazolopiperidone lactam is cytotoxic against tumors via inhibition of p53 interaction with murine double minute proteins","volume":"95\u201396","author":"Soares","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzym. Regul."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1111\/bph.14468","article-title":"Improving anticancer activity towards colon cancer cells with a new p53-activating agent","volume":"175","author":"Raimundo","year":"2018","journal-title":"Br. J. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ejps.2014.10.006","article-title":"Oxazoloisoindolinones with in vitro antitumor activity selectively activate a p53-pathway through potential inhibition of the p53-MDM2 interaction","volume":"66","author":"Soares","year":"2015","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/1878-0261.12051","article-title":"DIMP53-1: A novel small-molecule dual inhibitor of p53-MDM2\/X interactions with multifunctional p53-dependent anticancer properties","volume":"11","author":"Soares","year":"2017","journal-title":"Mol. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.neo.2018.06.008","article-title":"ETV7-Mediated DNAJC15 Repression Leads to Doxorubicin Resistance in Breast Cancer Cells","volume":"20","author":"Alessandrini","year":"2018","journal-title":"Neoplasia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-4939-7237-1_7","article-title":"Methods to Visualize MAVS Subcellular Localization","volume":"1656","author":"Vazquez","year":"2017","journal-title":"Methods Mol. Biol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/8\/1151\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:10:15Z","timestamp":1760188215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/8\/1151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,10]]},"references-count":52,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["cancers11081151"],"URL":"https:\/\/doi.org\/10.3390\/cancers11081151","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,10]]}}}