{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:54:23Z","timestamp":1792418063483,"version":"4.4.0"},"reference-count":77,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["CE200100012"],"award-info":[{"award-number":["CE200100012"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LE240100134"],"award-info":[{"award-number":["LE240100134"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T028254\/1"],"award-info":[{"award-number":["MR\/T028254\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/X001849\/1"],"award-info":[{"award-number":["BB\/X001849\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>MYC is an intrinsically disordered oncoprotein that drives cancer progression via widespread transcriptional dysregulation. Upon binding partner protein MAX, their basic\u2010helix1\u2010loop\u2010helix2\u2010Zip (bHLH\u2010Zip) domains assemble into an ordered heterodimer that binds E\u2010box DNA to promote cellular proliferation. This interface has been undruggable by small molecules. Here, we report a novel covalent downsizing strategy to inhibit MYC\u2010MAX interaction by targeting the C\u2010terminal Cys438 present in MYC, but absent in MAX and related proteins. Incorporating a mild acrylamide electrophile to covalently bond specifically with Cys438 enabled truncation of MAX to shorter peptides with high affinity for MYC. Using intracellular protein\u2010fragment complementation, MAX\u2010derived sequences were optimized for interaction with MYC. Further downsizing, inserting a helix\u2010inducing constraint, and optimal electrophile positioning produced a serum\u2010stable 24\u2010residue covalent inhibitor that captured endogenous MYC from cell lysates. Esterifying six Glu\/Asp residues enhanced membrane permeability, while intracellular esterolysis achieved robust cytosolic and nuclear accumulation of the MYC inhibitor. Microscopy confirmed nuclear delivery correlating directly with progressive loss of nuclear MYC. The esterified compound exhibited antiproliferative activity across MYC\u2010dependent cancer cell lines, inhibited migration, and triggered ubiquitin\u2010proteasome mediated MYC degradation, downregulating key target genes downstream of MYC. This covalent downsizing approach is a generalizable chemical strategy for targeting recalcitrant transcription factors.<\/jats:p>","DOI":"10.1002\/anie.4950007","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:13:43Z","timestamp":1792415623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Downsizing Electrophilic MAX\u2010Derived Helical Zipper Peptides to Covalently Bind and Degrade Oncogenic MYC"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-4050","authenticated-orcid":false,"given":"Aline Dantas","family":"de Araujo","sequence":"first","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Luo","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8633-3513","authenticated-orcid":false,"given":"Mahan","family":"Azad","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Bath  Bath, England United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4118-1958","authenticated-orcid":false,"given":"Jody M.","family":"Mason","sequence":"additional","affiliation":[{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Department of Life Sciences University of Bath  Bath, England United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-0704","authenticated-orcid":false,"given":"Junxian","family":"Lim","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-9930","authenticated-orcid":false,"given":"Timothy A.","family":"Hill","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-8566","authenticated-orcid":false,"given":"David P.","family":"Fairlie","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science Institute for Molecular Bioscience The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41571-021-00549-2","article-title":"The MYC Oncogene \u2014 The Grand Orchestrator of Cancer Growth and Immune Evasion","volume":"19","author":"Dhanasekaran R.","year":"2022","journal-title":"Nature Reviews Clinical Oncology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-020-00235-2","article-title":"Regulation of Cancer Cell Metabolism: Oncogenic MYC in the Driver's Seat","volume":"5","author":"Dong Y.","year":"2020","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41580-020-0215-2","article-title":"Target Gene\u2010independent Functions of MYC Oncoproteins","volume":"21","author":"Baluapuri A.","year":"2020","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2024.1342872","article-title":"MYC: There Is More to It than Cancer","volume":"12","author":"Zacar\u00edas\u2010Fluck M. F.","year":"2024","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41388-024-03174-2","article-title":"Transcriptional Regulation by MYC: An Emerging New Model","volume":"44","author":"Jakobsen S. T.","year":"2025","journal-title":"Oncogene"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41392-018-0008-7","article-title":"Targeting Oncogenic Myc as a Strategy for Cancer Treatment","volume":"3","author":"Chen H.","year":"2018","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12943-020-01291-6","article-title":"Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c\u2010Myc","volume":"20","author":"Madden S. K.","year":"2021","journal-title":"Molecular Cancer"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s41573-025-01143-2","article-title":"MYC in Cancer: From Undruggable Target to Clinical Trials","volume":"24","author":"Whitfield J. R.","year":"2025","journal-title":"Nature Reviews Drug Discovery"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41392-023-01589-z","article-title":"Recent Advances in Targeting the \u201cUndruggable\u201d Proteins: From Drug Discovery to Clinical Trials","volume":"8","author":"Xie X.","year":"2023","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1071489","article-title":"Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC","volume":"297","author":"Jain M.","year":"2002","journal-title":"Science"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202103090","article-title":"The Long Journey to Bring a Myc Inhibitor to the Clinic","volume":"220","author":"Whitfield J. R.","year":"2021","journal-title":"Journal of Cell Biology"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41591-024-02805-1","article-title":"MYC Targeting by OMO\u2010103 in Solid Tumors: A Phase 1 Trial","volume":"30","author":"Garralda E.","year":"2024","journal-title":"Nature Medicine"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nature07260","article-title":"Modelling Myc Inhibition as a Cancer Therapy","volume":"455","author":"Soucek L.","year":"2008","journal-title":"Nature"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2021.102154","article-title":"MYC as a Target for Cancer Treatment","volume":"94","author":"Duffy M. J.","year":"2021","journal-title":"Cancer Treatment Reviews"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.jconrel.2024.08.009","article-title":"EV20\/Omomyc: A novel dual MYC\/HER3 targeting immunoconjugate","volume":"374","author":"Bibb\u00f2 S.","year":"2024","journal-title":"Journal of Controlled Release"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.tcb.2022.07.006","article-title":"MYC: A Complex Problem","volume":"33","author":"Das S. K.","year":"2023","journal-title":"Trends in Cell Biology"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a014266","article-title":"Therapeutic Strategies to Inhibit MYC","volume":"4","author":"McKeown M. R.","year":"2014","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1158\/0008-5472.CAN-20-2959","article-title":"Turning up the Heat on MYC: Progress in Small\u2010Molecule Inhibitors","volume":"81","author":"Truica M. I.","year":"2021","journal-title":"Cancer Research"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"8869","DOI":"10.18632\/oncotarget.2588","article-title":"In Vivo Quantification and Perturbation of Myc\u2010Max Interactions and the Impact on Oncogenic Potential","volume":"5","author":"Raffeiner P.","year":"2014","journal-title":"Oncotarget"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116194","article-title":"MYC the Oncogene From Hell: Novel Opportunities for Cancer Therapy","volume":"267","author":"Papadimitropoulou A.","year":"2024","journal-title":"European Journal of Medicinal Chemistry"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"6038","DOI":"10.1016\/j.bmcl.2009.09.044","article-title":"Small Molecule Inhibitors of Myc\/Max Dimerization and Myc\u2010induced Cell Transformation","volume":"19","author":"Shi J.","year":"2009","journal-title":"Bioorganic and Medicinal Chemistry Letters"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/cmdc.200600294","article-title":"Selective Inhibition of c\u2010Myc\/Max Dimerization by a Pyrazolo[1,5\u2010 a ]Pyrimidine","volume":"2","author":"Kiessling A.","year":"2007","journal-title":"ChemMedChem"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.exphem.2006.06.019","article-title":"A Small\u2010molecule c\u2010Myc Inhibitor, 10058\u2010F4, Induces Cell\u2010cycle Arrest, Apoptosis, and Myeloid Differentiation of human Acute Myeloid Leukemia","volume":"34","author":"Huang M. J.","year":"2006","journal-title":"Experimental Hematology"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"7390","DOI":"10.1021\/ja900616b","article-title":"Multiple Independent Binding Sites for Small\u2010Molecule Inhibitors on the Oncoprotein c\u2010Myc","volume":"131","author":"Hammoudeh D. I.","year":"2009","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.bmcl.2012.10.013","article-title":"Pharmacophore Identification of c\u2010Myc Inhibitor 10074\u2010G5","volume":"23","author":"Yap J. L.","year":"2013","journal-title":"Bioorganic and Medicinal Chemistry Letters"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"12556","DOI":"10.1073\/pnas.1319488111","article-title":"Inhibitor of MYC Identified in a Kr\u00f6hnke Pyridine Library","volume":"111","author":"Hart J. R.","year":"2014","journal-title":"Proceedings of the National Academy of Science U S A"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1021\/acschembio.7b00799","article-title":"Targeted Disruption of Myc\u2013Max Oncoprotein Complex by a Small Molecule","volume":"12","author":"Choi S. H.","year":"2017","journal-title":"ACS Chemical Biology"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10549-022-06673-6","article-title":"MYC as a Therapeutic Target for the Treatment of Triple\u2010negative Breast Cancer: Preclinical Investigations with the Novel MYC Inhibitor, MYCi975","volume":"195","author":"Tang M.","year":"2022","journal-title":"Breast Cancer Research and Treatment"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s12964-022-00868-6","article-title":"Novel Dual\u2010targeting c\u2010Myc Inhibitor D347\u20102761 Represses Myeloma Growth via Blocking c\u2010Myc\/Max Heterodimerization and Disturbing Its Stability","volume":"20","author":"Yao R.","year":"2022","journal-title":"Cell Communication and Signaling"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103756","article-title":"Therapeutic Targeting of \u201cUndruggable\u201d MYC","volume":"75","author":"Llombart V.","year":"2022","journal-title":"EBioMedicine"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.113137","article-title":"Targeting MYC: From Understanding Its Biology to Drug Discovery","volume":"213","author":"Ross J.","year":"2021","journal-title":"European Journal of Medicinal Chemistry"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202416082","article-title":"Development of DuoMYC: A Synthetic Cell Penetrant Miniprotein That Efficiently Inhibits the Oncogenic Transcription Factor MYC","volume":"64","author":"Ellenbroek B. D.","year":"2025","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","first-page":"11788","DOI":"10.1021\/jacs.1c05666","article-title":"Engineering Bioactive Dimeric Transcription Factor Analogs via Palladium Rebound Reagents","volume":"143","author":"Jbara M.","year":"2021","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1021\/acscentsci.1c00663","article-title":"Parallel Automated Flow Synthesis of Covalent Protein Complexes That Can Inhibit MYC\u2010Driven Transcription","volume":"7","author":"Pomplun S.","year":"2021","journal-title":"ACS Central Science"},{"key":"e_1_2_8_36_1","first-page":"42647","article-title":"Chemical Engineering of Transcription Factors Uncovered Cell\u2010Permeable \u00b5Max Modulators","volume":"147","author":"Harel O.","year":"2025","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_37_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41587-022-01504-x","article-title":"Targeting MYC with Modular Synthetic Transcriptional Repressors Derived From bHLH DNA\u2010binding Domains","volume":"41","author":"Speltz T. E.","year":"2023","journal-title":"Nature Biotechnology"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2025.102839"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"14552","DOI":"10.1021\/jacs.8b08338","article-title":"Construction of a Sequenceable Protein Mimetic Peptide Library With a True 3D Diversifiable Chemical Space","volume":"140","author":"Li Z.","year":"2018","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1021\/jacs.3c09615","article-title":"MYC\u2010Targeting Inhibitors Generated From a Stereodiversified Bicyclic Peptide Library","volume":"146","author":"Li Z.","year":"2024","journal-title":"Journal of the American Chemical Society"},{"key":"e_1_2_8_41_1","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1158\/1538-7445.AM2021-2471","article-title":"Abstract 2471: IDP\u2010121, a First in Class Staple Peptide Targeting c\u2010MYC","volume":"81","author":"Calvis C.","year":"2021","journal-title":"Cancer Research"},{"key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"7875","DOI":"10.1038\/s41467-024-52202-y","article-title":"Targeted Transcriptional Downregulation of MYC Using Epigenomic Controllers Demonstrates Antitumor Activity in Hepatocellular Carcinoma Models","volume":"15","author":"Senapedis W.","year":"2024","journal-title":"Nature Communications"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2025.1601975","article-title":"Rethinking MYC Inhibition: A Multi\u2010dimensional Approach to Overcome Cancer's Master Regulator","volume":"13","author":"Yu J.","year":"2025","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"e_1_2_8_44_1","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202217716","article-title":"Chemical Synthesis of Bioactive Proteins","volume":"62","author":"Harel O.","year":"2023","journal-title":"Angewandte Chemie International Edition"},{"key":"e_1_2_8_45_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s42004-026-02033-3","article-title":"Advancing Protein Engineering via Organic Chemistry","volume":"9","author":"Nithun R. V.","year":"2026","journal-title":"Communications Chemistry"},{"key":"e_1_2_8_46_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107137","article-title":"Therapeutic Stapled Peptides: Efficacy and Molecular Targets","volume":"203","author":"Li Y.","year":"2024","journal-title":"Pharmacological Research"},{"key":"e_1_2_8_47_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0092-8674(02)01284-9","article-title":"X\u2010Ray Structures of Myc\u2010Max and Mad\u2010Max Recognizing DNA","volume":"112","author":"Nair S. K.","year":"2003","journal-title":"Cell"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1126\/science.2006410","article-title":"Max: A Helix\u2010Loop\u2010Helix Zipper Protein That Forms a Sequence\u2010Specific DNA\u2010Binding Complex with Myc","volume":"251","author":"Blackwood E. M.","year":"1991","journal-title":"Science"},{"key":"e_1_2_8_49_1","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1073\/pnas.062036999","article-title":"Small\u2010molecule Antagonists of Myc\/Max Dimerization Inhibit Myc\u2010induced Transformation of Chicken Embryo Fibroblasts","volume":"99","author":"Berg T.","year":"2002","journal-title":"Proceedings of the National Academy of Science U S A"},{"key":"e_1_2_8_50_1","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1021\/acs.jmedchem.8b00010","article-title":"Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl\u20101 Proteins","volume":"61","author":"Araujo A. D.","year":"2018","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_8_51_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1021\/acsmedchemlett.6b00395","article-title":"Electrophilic Helical Peptides That Bond Covalently, Irreversibly, and Selectively in a Protein\u2013Protein Interaction Site","volume":"8","author":"Araujo A. D.","year":"2017","journal-title":"ACS Medicinal Chemistry Letters"},{"key":"e_1_2_8_52_1","doi-asserted-by":"crossref","first-page":"13554","DOI":"10.1021\/bi00041a035","article-title":"The Leucine Zippers of the HLH\u2010LZ Proteins Max and c\u2010Myc Preferentially Form Heterodimers","volume":"34","author":"Muhle\u2010Goll C.","year":"1995","journal-title":"Biochemistry"},{"key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3390\/cells9040883","article-title":"Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc","volume":"9","author":"Mass\u00f3\u2010Vall\u00e9s D.","year":"2020","journal-title":"Cells"},{"key":"e_1_2_8_54_1","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1021\/bi602506p","article-title":"Positive Aspects of Negative Design:\u2009 Simultaneous Selection of Specificity and Interaction Stability","volume":"46","author":"Mason J. M.","year":"2007","journal-title":"Biochemistry"},{"key":"e_1_2_8_55_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1021\/acschembio.3c00779","article-title":"Exponential Combination of a and E\/G Intracellular Peptide Libraries Identifies a Selective ATF3 Inhibitor","volume":"19","author":"Yu M.","year":"2024","journal-title":"ACS Chemical Biology"},{"key":"e_1_2_8_56_1","doi-asserted-by":"crossref","first-page":"8989","DOI":"10.1073\/pnas.0509880103","article-title":"Semirational Design of Jun\u2010Fos Coiled Coils With Increased Affinity: Universal Implications for Leucine Zipper Prediction and Design","volume":"103","author":"Mason J. M.","year":"2006","journal-title":"Proceedings of the National Academy of Science U S A"},{"key":"e_1_2_8_57_1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1039\/D1CB00012H","article-title":"Combined Computational and Intracellular Peptide Library Screening: Towards a Potent and Selective Fra1 Inhibitor","volume":"2","author":"Yu M.","year":"2021","journal-title":"RSC Chemical Biology"},{"key":"e_1_2_8_58_1","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1021\/acschembio.7b00303","article-title":"Downsizing Proto\u2010oncogene cFos to Short Helix\u2010Constrained Peptides That Bind Jun","volume":"12","author":"Baxter D.","year":"2017","journal-title":"ACS Chemical Biology"},{"key":"e_1_2_8_59_1","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1021\/jacsau.2c00105","article-title":"An Approach to Derive Functional Peptide Inhibitors of Transcription Factor Activity","volume":"2","author":"Brennan A.","year":"2022","journal-title":"JACS Au"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202416963","article-title":"An Intracellular Peptide Library Screening Platform Identifies Irreversible Covalent Transcription Factor Inhibitors","volume":"12","author":"Brennan A.","year":"2025","journal-title":"Advanced Science"},{"key":"e_1_2_8_61_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/cbic.200300781","article-title":"Coiled Coil Domains: Stability, Specificity, and Biological Implications","volume":"5","author":"Mason J. M.","year":"2004","journal-title":"ChemBioChem"},{"key":"e_1_2_8_62_1","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1006\/jmbi.1998.1762","article-title":"Inter\u2010helical Interactions in the Leucine Zipper Coiled Coil Dimer: Ph and Salt Dependence of Coupling Energy between Charged Amino Acids","volume":"279","author":"Krylov D.","year":"1998","journal-title":"Journal of Molecular Biology"},{"key":"e_1_2_8_63_1","doi-asserted-by":"crossref","first-page":"13703","DOI":"10.1073\/pnas.96.24.13703","article-title":"Efficient Folding of Proteins With Multiple Disulfide Bonds in the Escherichia coli Cytoplasm","volume":"96","author":"Bessette P. H.","year":"1999","journal-title":"Proceedings of the National Academy of Science U S A"},{"key":"e_1_2_8_64_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nsb0694-399","article-title":"Elucidating the folding problem of helical peptides using empirical parameters","volume":"1","author":"Mu\u00f1oz V.","year":"1994","journal-title":"Nature Structural Biology"},{"key":"e_1_2_8_65_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1233606","article-title":"Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay","volume":"341","author":"Molina D. M.","year":"2013","journal-title":"Science"},{"key":"e_1_2_8_66_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1039\/D4ME00072B","article-title":"Multi\u2010site Esterification: A Tunable, Reversible Strategy to Tailor Therapeutic Peptides for Delivery","volume":"9","author":"Bannon M. S.","year":"2024","journal-title":"Molecular Systems Design and Engineering"},{"key":"e_1_2_8_67_1","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1021\/acschembio.0c00218","article-title":"Improving Membrane Permeation in the beyond Rule\u2010of\u2010Five Space by Using Prodrugs to Mask Hydrogen Bond Donors","volume":"15","author":"Barlow N.","year":"2020","journal-title":"ACS Chemical Biology"},{"key":"e_1_2_8_68_1","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1021\/acs.molpharmaceut.8b00466","article-title":"Enhancing Oral Bioavailability of Cyclic RGD Hexa\u2010peptides by the Lipophilic Prodrug Charge Masking Approach: Redirection of Peptide Intestinal Permeability From a Paracellular to Transcellular Pathway","volume":"15","author":"Schumacher\u2010Klinger A.","year":"2018","journal-title":"Molecular Pharmaceutics"},{"key":"e_1_2_8_69_1","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0960-894X(03)00081-7","article-title":"Prodrugs to Enhance central Nervous System Effects of the TRH\u2010like Peptide pGlu\u2010Glu\u2010Pro\u2010NH2","volume":"13","author":"Prokai\u2010Tatrai K.","year":"2003","journal-title":"Bioorganic and Medicinal Chemistry Letters"},{"key":"e_1_2_8_70_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.3390\/molecules14020633","article-title":"Prodrugs of Thyrotropin\u2010Releasing Hormone and Related Peptides as Central Nervous System Agents","volume":"14","author":"Prokai\u2010Tatrai K.","year":"2009","journal-title":"Molecules"},{"key":"e_1_2_8_71_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/bip.21418","article-title":"Synthesis and Characterization of Ester\u2010Based Prodrugs of Glucagon\u2010like Peptide 1","volume":"94","author":"De A.","year":"2010","journal-title":"Biopolymers"},{"key":"e_1_2_8_72_1","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0092-8674(84)90457-4","article-title":"A Short Amino Acid Sequence Able to Specify Nuclear Location","volume":"39","author":"Kalderon D.","year":"1984","journal-title":"Cell"},{"key":"e_1_2_8_73_1","article-title":"Intrinsic Cell\u2010penetrating Activity Propels Omomyc From Proof of Concept to Viable Anti\u2010MYC Therapy","volume":"11","author":"Beaulieu M.\u2010E.","year":"2019","journal-title":"Science Translational Medicine"},{"key":"e_1_2_8_74_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41419-021-03685-w","article-title":"Directly Targeting c\u2010Myc Contributes to the Anti\u2010multiple Myeloma Effect of anlotinib","volume":"12","author":"Cao Y.","year":"2021","journal-title":"Cell Death and Disease"},{"key":"e_1_2_8_75_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.chembiol.2020.09.001","article-title":"Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC","volume":"28","author":"Boike L.","year":"2021","journal-title":"Cell Chemical Biology"},{"key":"e_1_2_8_76_1","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1021\/acs.biochem.4c00446","article-title":"Mammalian Esterase Activity: Implications for Peptide Prodrugs","volume":"63","author":"Petri Y. D.","year":"2024","journal-title":"Biochemistry"},{"key":"e_1_2_8_77_1","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1128\/MCB.20.7.2423-2435.2000","article-title":"c\u2010Myc Proteolysis by the Ubiquitin\u2010Proteasome Pathway: Stabilization of c\u2010Myc in Burkitt's Lymphoma Cells","volume":"20","author":"Gregory M. A.","year":"2000","journal-title":"Molecular and Cellular Biology"},{"key":"e_1_2_8_78_1","doi-asserted-by":"crossref","DOI":"10.1002\/anie.202508518","article-title":"Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC","volume":"64","author":"Rosen H. T.","year":"2025","journal-title":"Angewandte Chemie International Edition"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.4950007","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.4950007","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.4950007","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.4950007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:13:52Z","timestamp":1792415632000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.4950007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":77,"alternative-id":["10.1002\/anie.4950007"],"URL":"https:\/\/doi.org\/10.1002\/anie.4950007","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"assertion":[{"value":"2026-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4950007"}}