{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:41:55Z","timestamp":1788572515639,"version":"build-2803163510"},"reference-count":104,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100020581","name":"AIRC Foundation for Cancer Research","doi-asserted-by":"publisher","award":["IG29329"],"award-info":[{"award-number":["IG29329"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"AIRC Foundation for Cancer Research","doi-asserted-by":"publisher","award":["IG20801"],"award-info":[{"award-number":["IG20801"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"AIRC Foundation for Cancer Research","doi-asserted-by":"publisher","award":["MFAG 2021-ID 26536"],"award-info":[{"award-number":["MFAG 2021-ID 26536"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"AIRC Foundation for Cancer Research","doi-asserted-by":"publisher","award":["IG23099"],"award-info":[{"award-number":["IG23099"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"AIRC Foundation for Cancer Research","doi-asserted-by":"publisher","award":["IG24345"],"award-info":[{"award-number":["IG24345"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004588","name":"Istituto Pasteur-Fondazione Cenci Bolognetti","doi-asserted-by":"publisher","award":["3175\/2021 E DD"],"award-info":[{"award-number":["3175\/2021 E DD"]}],"id":[{"id":"10.13039\/501100004588","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PRIN 2022MXFLMZ"],"award-info":[{"award-number":["PRIN 2022MXFLMZ"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["P2022JZ9RE"],"award-info":[{"award-number":["P2022JZ9RE"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003762","name":"Institut Pasteur","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.ymthe.2025.10.036","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T16:08:13Z","timestamp":1760803693000},"page":"582-605","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of a new selective ERAP1 inhibitor for Hedgehog-dependent cancer treatment"],"prefix":"10.1016","volume":"34","author":[{"given":"Francesca","family":"Bufalieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Cucinotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cammarone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Agnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Basili","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ferri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Quaglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Laura","family":"Capriotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela Maria","family":"Montone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Lospinoso Severini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Tempora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Juretich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta S.","family":"Semrau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Navacci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilisa","family":"Conenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bordone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Spallotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Garavaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Storici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ghirga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Lagan\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Ayrault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Infante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Botta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doriana","family":"Fruci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Di Marcotullio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2025.10.036_bib1","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1200\/JCO.2017.72.7842","article-title":"Medulloblastoma: From Myth to Molecular","volume":"35","author":"Ramaswamy","year":"2017","journal-title":"JCO"},{"key":"10.1016\/j.ymthe.2025.10.036_bib2","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrm3598","article-title":"The mechanisms of Hedgehog signalling and its roles in development and disease","volume":"14","author":"Briscoe","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib3","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1126\/science.1233009","article-title":"Genomic Analysis of Non- NF2 Meningiomas Reveals Mutations in TRAF7 , KLF4 , AKT1 , and SMO","volume":"339","author":"Clark","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.10.036_bib4","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1126\/science.1164368","article-title":"Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses","volume":"321","author":"Jones","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.10.036_bib5","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1158\/1078-0432.CCR-09-2570","article-title":"The Role of the Hedgehog Signaling Pathway in the Development of Basal Cell Carcinoma and Opportunities for Treatment","volume":"16","author":"Caro","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib6","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.15252\/embj.201593374","article-title":"SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development","volume":"35","author":"Raducu","year":"2016","journal-title":"EMBO J."},{"key":"10.1016\/j.ymthe.2025.10.036_bib7","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc796","article-title":"Gli and hedgehog in cancer: tumours, embryos and stem cells","volume":"2","author":"Ruiz I Altaba","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ymthe.2025.10.036_bib8","doi-asserted-by":"crossref","first-page":"19320","DOI":"10.1074\/jbc.M513203200","article-title":"Gli2 Is Targeted for Ubiquitination and Degradation by \u03b2-TrCP Ubiquitin Ligase","volume":"281","author":"Bhatia","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib9","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1101\/gad.1380906","article-title":"Dual degradation signals control Gli protein stability and tumor formation","volume":"20","author":"Huntzicker","year":"2006","journal-title":"Genes Dev."},{"key":"10.1016\/j.ymthe.2025.10.036_bib10","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1128\/MCB.26.9.3365-3377.2006","article-title":"Sonic hedgehog Signaling Regulates Gli2 Transcriptional Activity by Suppressing Its Processing and Degradation","volume":"26","author":"Pan","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib11","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1080\/10286020802277956","article-title":"Canthin-6-one alkaloids from Picrasma quassioides and their cytotoxic activity","volume":"10","author":"Jiang","year":"2008","journal-title":"J. Asian Nat. Prod. Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib12","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1038\/s41467-018-03339-0","article-title":"Itch\/\u03b2-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis","volume":"9","author":"Infante","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.10.036_bib13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1101\/gad.1902910","article-title":"The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins","volume":"24","author":"Humke","year":"2010","journal-title":"Genes Dev."},{"key":"10.1016\/j.ymthe.2025.10.036_bib14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1073\/pnas.0509927103","article-title":"Evidence for the direct involvement of \u03b2TrCP in Gli3 protein processing","volume":"103","author":"Wang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.10.036_bib15","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.ccell.2014.11.015","article-title":"SnapShot: Medulloblastoma","volume":"26","author":"Rusert","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2025.10.036_bib16","doi-asserted-by":"crossref","first-page":"re6","DOI":"10.1126\/scisignal.2002906","article-title":"The Hedgehog Signal Transduction Network","volume":"5","author":"Robbins","year":"2012","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ymthe.2025.10.036_bib17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.devcel.2016.07.026","article-title":"Hedgehog Signal Transduction: Key Players, Oncogenic Drivers, and Cancer Therapy","volume":"38","author":"Pak","year":"2016","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ymthe.2025.10.036_bib18","doi-asserted-by":"crossref","first-page":"4869","DOI":"10.4049\/jimmunol.176.8.4869","article-title":"Expression of Endoplasmic Reticulum Aminopeptidases in EBV-B Cell Lines from Healthy Donors and in Leukemia\/Lymphoma, Carcinoma, and Melanoma Cell Lines","volume":"176","author":"Fruci","year":"2006","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib19","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/jcp.21454","article-title":"Altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues","volume":"216","author":"Fruci","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib20","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1186\/s13046-024-03180-y","article-title":"Combining ERAP1 silencing and entinostat therapy to overcome resistance to cancer immunotherapy in neuroblastoma","volume":"43","author":"Tempora","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib21","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1038\/s41467-019-11093-0","article-title":"ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of \u03b2TrCP","volume":"10","author":"Bufalieri","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.10.036_bib22","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.948297","article-title":"Targeting the antigen processing and presentation pathway to overcome resistance to immune checkpoint therapy","volume":"13","author":"D\u2019Amico","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib23","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.3389\/fimmu.2018.02463","article-title":"How ERAP1 and ERAP2 Shape the Peptidomes of Disease-Associated MHC-I Proteins","volume":"9","author":"L\u00f3pez de Castro","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.trecan.2021.09.005","article-title":"ERAP1 as an emerging therapeutic target for medulloblastoma","volume":"8","author":"Bufalieri","year":"2022","journal-title":"Trends Cancer"},{"key":"10.1016\/j.ymthe.2025.10.036_bib25","doi-asserted-by":"crossref","first-page":"11597","DOI":"10.1021\/acs.jmedchem.4c00840","article-title":"ERAP Inhibitors in Autoimmunity and Immuno-Oncology: Medicinal Chemistry Insights","volume":"67","author":"Fougiaxis","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib26","first-page":"387","article-title":"Alkaloids of the Australian Rutaceae: Pentaceras australis Hook. F. I. Isolation of the Alkaloids and Identification of Canthin-6-one","volume":"5","author":"Haynes","year":"1952","journal-title":"Aust. J. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib27","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1107\/S1744309112006963","article-title":"Crystallization and preliminary X-ray diffraction analysis of human endoplasmic reticulum aminopeptidase 2","volume":"68","author":"Ascher","year":"2012","journal-title":"Acta Crystallogr. F Struct. Biol. Cryst. Commun."},{"key":"10.1016\/j.ymthe.2025.10.036_bib28","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1039\/D0QO01210F","article-title":"A unique high-diversity natural product collection as a reservoir of new therapeutic leads","volume":"8","author":"Ghirga","year":"2021","journal-title":"Org. Chem. Front."},{"key":"10.1016\/j.ymthe.2025.10.036_bib29","first-page":"759","article-title":"Study on Pharmacokinetics of p-Coumaric Acid in Baihuasheshecao Injection","volume":"25","year":"2005","journal-title":"Chin. J. Pharm. Anal."},{"key":"10.1016\/j.ymthe.2025.10.036_bib30","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1016\/0040-4020(79)87031-3","article-title":"Ferruginin A and B and ferruanthrone, new triprenylated anthranoids from Vismia baccifera var. ferruginea","volume":"35","author":"Monache","year":"1979","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ymthe.2025.10.036_bib31","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10722-011-9660-2","article-title":"Screening species of Pilocarpus (Rutaceae) as sources of pilocarpine and other imidazole alkaloids","volume":"58","author":"Sawaya","year":"2011","journal-title":"Genet. Resour. Crop Evol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib32","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1002\/cbdv.201000323","article-title":"Chemical Constituents of Plants from the Genus Simaba (Simaroubaceae)","volume":"8","author":"Barbosa","year":"2011","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.ymthe.2025.10.036_bib33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.phytochem.2011.12.022","article-title":"Oleanolic acid","volume":"77","author":"Pollier","year":"2012","journal-title":"Phytochemistry"},{"key":"10.1016\/j.ymthe.2025.10.036_bib34","first-page":"176","article-title":"Chemical constituents from Aegle marmelos","volume":"22","author":"Laphookhieo","year":"2012","journal-title":"J. Braz. Chem. Soc."},{"key":"10.1016\/j.ymthe.2025.10.036_bib35","doi-asserted-by":"crossref","first-page":"201386","DOI":"10.1155\/2015\/201386","article-title":"Isolation, Characterization, and RP-HPLC Estimation of P-Coumaric Acid from Methanolic Extract of Durva Grass ( Cynodon dactylon Linn.) (Pers.)","volume":"2015","author":"Karthikeyan","year":"2015","journal-title":"Int. J. Anal. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib36","doi-asserted-by":"crossref","first-page":"578107","DOI":"10.1155\/2015\/578107","article-title":"Rhein: A Review of Pharmacological Activities","volume":"2015","author":"Zhou","year":"2015","journal-title":"Evid. Based. Complement. Alternat. Med."},{"key":"10.1016\/j.ymthe.2025.10.036_bib37","doi-asserted-by":"crossref","first-page":"240","DOI":"10.20307\/nps.2021.27.4.240","article-title":"Chemical Constituents from Aegle marmelos Fruits","volume":"27","author":"Kim","year":"2021","journal-title":"nps."},{"key":"10.1016\/j.ymthe.2025.10.036_bib38","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.3390\/molecules26133827","article-title":"Recent Developments in Therapeutic and Nutraceutical Applications of p-Methoxycinnamic Acid from Plant Origin","volume":"26","author":"P\u0142owuszy\u0144ska","year":"2021","journal-title":"Molecules"},{"key":"10.1016\/j.ymthe.2025.10.036_bib39","article-title":"Review on canthin-6-one alkaloids: Distribution, chemical aspects and biological activities","volume":"5","author":"Farouil","year":"2022","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"10.1016\/j.ymthe.2025.10.036_bib40","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.3390\/metabo12111145","article-title":"Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review","volume":"12","author":"Muruganathan","year":"2022","journal-title":"Metabolites"},{"key":"10.1016\/j.ymthe.2025.10.036_bib41","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.3390\/plants11223091","article-title":"Acacia catechu (L.f.) Willd.: A Review on Bioactive Compounds and Their Health Promoting Functionalities","volume":"11","author":"Kumari","year":"2022","journal-title":"Plants"},{"key":"10.1016\/j.ymthe.2025.10.036_bib42","doi-asserted-by":"crossref","first-page":"7","DOI":"10.53879\/id.60.12.12905","article-title":"CINNAMIC ACID AND ITS DERIVATIVES AS POTENTIAL ANTI-TUBERCULAR AGENTS","volume":"60","author":"Thakar","year":"2023","journal-title":"IND. DRU."},{"key":"10.1016\/j.ymthe.2025.10.036_bib43","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.4049\/jimmunol.175.10.6605","article-title":"Leucine Aminopeptidase Is Not Essential for Trimming Peptides in the Cytosol or Generating Epitopes for MHC Class I Antigen Presentation","volume":"175","author":"Towne","year":"2005","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib44","doi-asserted-by":"crossref","first-page":"9202","DOI":"10.1073\/pnas.0603095103","article-title":"Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance","volume":"103","author":"York","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.10.036_bib45","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.4049\/jimmunol.1300220","article-title":"Induction of Protective Antitumor Immunity through Attenuation of ERAAP Function","volume":"190","author":"James","year":"2013","journal-title":"J. Immunol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib46","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1158\/0008-5472.CAN-14-1643","article-title":"ERAP1 regulates natural killer cell function by controlling the engagement of inhibitory receptors","volume":"75","author":"Cifaldi","year":"2015","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib47","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1021\/acsmedchemlett.4c00401","article-title":"Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design","volume":"15","author":"Hryczanek","year":"2024","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ymthe.2025.10.036_bib48","series-title":"Assay Guidance Manual","article-title":"Screening for Target Engagement using the Cellular Thermal Shift Assay - CETSA","author":"Axelsson","year":"2004"},{"key":"10.1016\/j.ymthe.2025.10.036_bib49","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/35023008","article-title":"Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine","volume":"406","author":"Taipale","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.10.036_bib50","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1101\/gad.1025302","article-title":"Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened","volume":"16","author":"Chen","year":"2002","journal-title":"Genes Dev."},{"key":"10.1016\/j.ymthe.2025.10.036_bib51","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1126\/science.277.5329.1109","article-title":"Altered Neural Cell Fates and Medulloblastoma in Mouse patched Mutants","volume":"277","author":"Goodrich","year":"1997","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.10.036_bib52","doi-asserted-by":"crossref","first-page":"7745","DOI":"10.1073\/pnas.1101262108","article-title":"Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming","volume":"108","author":"Kochan","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.10.036_bib53","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nsmb.2021","article-title":"Structural basis for antigenic peptide precursor processing by the endoplasmic reticulum aminopeptidase ERAP1","volume":"18","author":"Nguyen","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0896-6273(00)80682-0","article-title":"Control of Neuronal Precursor Proliferation in the Cerebellum by Sonic Hedgehog","volume":"22","author":"Wechsler-Reya","year":"1999","journal-title":"Neuron"},{"key":"10.1016\/j.ymthe.2025.10.036_bib55","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ccr.2008.07.005","article-title":"Acquisition of Granule Neuron Precursor Identity Is a Critical Determinant of Progenitor Cell Competence to Form Shh-Induced Medulloblastoma","volume":"14","author":"Sch\u00fcller","year":"2008","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2025.10.036_bib56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41419-020-03307-x","article-title":"MEX3A contributes to development and progression of glioma through regulating cell proliferation and cell migration and targeting CCL2","volume":"12","author":"Yang","year":"2021","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ymthe.2025.10.036_bib57","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1084\/jem.20052271","article-title":"In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules","volume":"203","author":"Yan","year":"2006","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.ymthe.2025.10.036_bib58","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1007\/s00401-017-1753-3","article-title":"Medulloblastoma: experimental models and reality","volume":"134","author":"Neumann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib59","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4103\/1793-5482.151516","article-title":"Medulloblastoma: A common pediatric tumor: Prognostic factors and predictors of outcome","volume":"10","author":"Kumar","year":"2015","journal-title":"Asian J. Neurosurg."},{"key":"10.1016\/j.ymthe.2025.10.036_bib60","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11060-013-1216-1","article-title":"Neuropilin-2 contributes to tumorigenicity in a mouse model of Hedgehog pathway medulloblastoma","volume":"115","author":"Hayden Gephart","year":"2013","journal-title":"J. Neurooncol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib61","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nm.3613","article-title":"Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition","volume":"20","author":"Tang","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.10.036_bib62","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/15242","article-title":"Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice","volume":"5","author":"Aszterbaum","year":"1999","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.10.036_bib63","doi-asserted-by":"crossref","first-page":"200","DOI":"10.15252\/embj.201489213","article-title":"Gli1\/DNA interaction is a druggable target for Hedgehog-dependent tumors","volume":"34","author":"Infante","year":"2015","journal-title":"EMBO J."},{"key":"10.1016\/j.ymthe.2025.10.036_bib64","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.ccr.2008.07.003","article-title":"Medulloblastoma Can Be Initiated by Deletion of Patched in Lineage-Restricted Progenitors or Stem Cells","volume":"14","author":"Yang","year":"2008","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ymthe.2025.10.036_bib65","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1158\/0008-5472.CAN-05-4505","article-title":"Shh Pathway Activity Is Down-Regulated in Cultured Medulloblastoma Cells: Implications for Preclinical Studies","volume":"66","author":"Sasai","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib66","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.canlet.2012.07.010","article-title":"Medulloblastoma stem cells: Modeling tumor heterogeneity","volume":"338","author":"Manoranjan","year":"2013","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ymthe.2025.10.036_bib67","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1158\/1078-0432.CCR-14-0507","article-title":"Molecular Pathways: Novel Approaches for Improved Therapeutic Targeting of Hedgehog Signaling in Cancer Stem Cells","volume":"21","author":"Justilien","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib68","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.3390\/cancers7030851","article-title":"Hedgehog Signaling in the Maintenance of Cancer Stem Cells","volume":"7","author":"Cochrane","year":"2015","journal-title":"Cancers"},{"key":"10.1016\/j.ymthe.2025.10.036_bib69","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/aps.2013.27","article-title":"Understanding and targeting cancer stem cells: therapeutic implications and challenges","volume":"34","author":"Chen","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ymthe.2025.10.036_bib70","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1158\/0008-5472.CAN-16-1836","article-title":"ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas","volume":"77","author":"Grausam","year":"2017","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib71","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1016\/j.bmcl.2009.08.049","article-title":"GDC-0449\u2014A potent inhibitor of the hedgehog pathway","volume":"19","author":"Robarge","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ymthe.2025.10.036_bib72","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/bjc.2014.380","article-title":"Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells","volume":"111","author":"Valenzuela","year":"2014","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.ymthe.2025.10.036_bib73","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/01.JAA.0000524717.71084.50","article-title":"Understanding medulloblastoma","volume":"30","author":"Quinlan","year":"2017","journal-title":"JAAPA"},{"key":"10.1016\/j.ymthe.2025.10.036_bib74","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro. Oncol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib75","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3390\/cancers8020022","article-title":"Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors","volume":"8","author":"Rimkus","year":"2016","journal-title":"Cancers"},{"key":"10.1016\/j.ymthe.2025.10.036_bib76","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aaf7593","article-title":"Molecular mechanisms and therapeutic targets in pediatric brain tumors","volume":"10","author":"Liu","year":"2017","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ymthe.2025.10.036_bib77","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41418-023-01246-6","article-title":"SALL4 is a CRL3REN\/KCTD11 substrate that drives Sonic Hedgehog-dependent medulloblastoma","volume":"31","author":"Lospinoso Severini","year":"2024","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.ymthe.2025.10.036_bib78","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/14728222.2020.1751821","article-title":"ERAP1: a potential therapeutic target for a myriad of diseases","volume":"24","author":"Reeves","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.ymthe.2025.10.036_bib79","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1158\/0008-5472.CAN-10-3326","article-title":"Natural Killer Cells Efficiently Reject Lymphoma Silenced for the Endoplasmic Reticulum Aminopeptidase Associated with Antigen Processing","volume":"71","author":"Cifaldi","year":"2011","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib80","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.drudis.2015.01.009","article-title":"An analysis of FDA-approved drugs: natural products and their derivatives","volume":"21","author":"Patridge","year":"2016","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ymthe.2025.10.036_bib81","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.tips.2009.03.007","article-title":"Mechanisms of Hedgehog pathway activation in cancer and implications for therapy","volume":"30","author":"Scales","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ymthe.2025.10.036_bib82","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1080\/14728222.2020.1823967","article-title":"The SHH\/GLI signaling pathway: a therapeutic target for medulloblastoma","volume":"24","author":"Lospinoso Severini","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"10.1016\/j.ymthe.2025.10.036_bib83","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fphar.2019.00016","article-title":"Canthin-6-One Accelerates Alpha-Synuclein Degradation by Enhancing UPS Activity: Drug Target Identification by CRISPR-Cas9 Whole Genome-Wide Screening Technology","volume":"10","author":"Yuan","year":"2019","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ymthe.2025.10.036_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2021.112439","article-title":"A canthin-6-one derivative induces cell death by apoptosis\/necroptosis-like with DNA damage in acute myeloid cells","volume":"145","author":"Torquato","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ymthe.2025.10.036_bib85","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.bbagen.2017.01.033","article-title":"Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells","volume":"1861","author":"Vieira Torquato","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"10.1016\/j.ymthe.2025.10.036_bib86","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.3390\/molecules28083381","article-title":"Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators","volume":"28","author":"Zhang","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.ymthe.2025.10.036_bib87","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1055\/s-0031-1298322","article-title":"Carboline Alkaloids from Psammosilene tunicoides and Their Cytotoxic Activities","volume":"78","author":"Tian","year":"2012","journal-title":"Planta Med."},{"key":"10.1016\/j.ymthe.2025.10.036_bib88","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1021\/np500516v","article-title":"Canthin-6-one Displays Antiproliferative Activity and Causes Accumulation of Cancer Cells in the G2\/M Phase","volume":"77","author":"Dejos","year":"2014","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ymthe.2025.10.036_bib89","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1021\/ci100436p","article-title":"FRED Pose Prediction and Virtual Screening Accuracy","volume":"51","author":"McGann","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ymthe.2025.10.036_bib90","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s10822-012-9584-8","article-title":"FRED and HYBRID docking performance on standardized datasets","volume":"26","author":"McGann","year":"2012","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"10.1016\/j.ymthe.2025.10.036_bib91","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1021\/ci100031x","article-title":"Conformer Generation with OMEGA: Algorithm and Validation Using High Quality Structures from the Protein Databank and Cambridge Structural Database","volume":"50","author":"Hawkins","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ymthe.2025.10.036_bib92","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1021\/acs.jnatprod.2c00736","article-title":"Evaluating the in Vitro Efficacy of Quassinoids from Eurycoma longifolia and Eurycoma harmandiana against Common Cold Human Coronavirus OC43 and SARS-CoV-2 Using In-Cell Enzyme-Linked Immunosorbent Assay","volume":"85","author":"Choonong","year":"2022","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ymthe.2025.10.036_bib93","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1080\/14786419.2018.1434647","article-title":"Secondary metabolites from the unique bamboo, Melocanna baccifera","volume":"33","author":"Govindan","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib94","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1021\/acs.jnatprod.1c00146","article-title":"Tulipiferamide A, an Alkamide from Liriodendron tulipifera , Exhibits an Anti-Inflammatory Effect via Targeting IKK\u03b2 Phosphorylation","volume":"84","author":"Park","year":"2021","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ymthe.2025.10.036_bib95","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1080\/14786419.2016.1198351","article-title":"Chemical constituents from Agrimonia pilosa Ledeb. and their chemotaxonomic significance","volume":"30","author":"Liu","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"10.1016\/j.ymthe.2025.10.036_bib96","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1021\/np4005163","article-title":"Examination of the Phenolic Profile and Antioxidant Activity of the Leaves of the Australian Native Plant Smilax glyciphylla","volume":"76","author":"Huang","year":"2013","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ymthe.2025.10.036_bib97","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202304861","article-title":"Photosynthetic Fixation of CO2 in Alkenes by Heterogeneous Photoredox Catalysis with Visible Light","volume":"62","author":"Yuan","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ymthe.2025.10.036_bib98","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115895","article-title":"Anti-adipogenic action of a novel oxazole derivative through activation of AMPK pathway","volume":"262","author":"Mishra","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib99","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1021\/jo00057a031","article-title":"An effective chirospecific synthesis of (+)-pilocarpine from L-aspartic acid","volume":"58","author":"Dener","year":"1993","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ymthe.2025.10.036_bib100","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1107\/S1600576720013412","article-title":"ATSAS 3.0 : expanded functionality and new tools for small-angle scattering data analysis","volume":"54","author":"Manalastas-Cantos","year":"2021","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.ymthe.2025.10.036_bib101","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1107\/S0021889809000338","article-title":"DAMMIF , a program for rapid ab-initio shape determination in small-angle scattering","volume":"42","author":"Franke","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.ymthe.2025.10.036_bib102","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1107\/S0021889892001663","article-title":"Determination of the regularization parameter in indirect-transform methods using perceptual criteria","volume":"25","author":"Svergun","year":"1992","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.ymthe.2025.10.036_bib103","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s12161-017-0999-7","article-title":"Label-Free Shotgun Proteomics Approach to Characterize Muscle Tissue from Farmed and Wild European Sea Bass (Dicentrarchus labrax)","volume":"11","author":"Chiozzi","year":"2018","journal-title":"Food Anal. Methods"},{"key":"10.1016\/j.ymthe.2025.10.036_bib104","doi-asserted-by":"crossref","first-page":"13117","DOI":"10.1021\/acs.analchem.2c02549","article-title":"Novel Aza-Patern\u00f2-B\u00fcchi Reaction Allows Pinpointing Carbon\u2013Carbon Double Bonds in Unsaturated Lipids by Higher Collisional Dissociation","volume":"94","author":"Cerrato","year":"2022","journal-title":"Anal. Chem."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625008573?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625008573?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T19:29:00Z","timestamp":1783020540000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001625008573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":104,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S1525001625008573"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.10.036","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of a new selective ERAP1 inhibitor for Hedgehog-dependent cancer treatment","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.10.036","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}