{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:10:31Z","timestamp":1793661031815,"version":"4.5.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,28]],"date-time":"2024-01-28T00:00:00Z","timestamp":1706400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.ejmech.2024.116167","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T11:33:54Z","timestamp":1706528034000},"page":"116167","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":28,"special_numbering":"C","title":["Design, synthesis, and biological characterization of proteolysis targeting chimera (PROTACs) for the ataxia telangiectasia and RAD3-related (ATR) kinase"],"prefix":"10.1016","volume":"267","author":[{"given":"Abdallah M.","family":"Alfayomy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy","family":"Ashry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita G.","family":"Kansy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Christin","family":"Sarnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Erdmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver H.","family":"Kr\u00e4mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-9261","authenticated-orcid":false,"given":"Wolfgang","family":"Sippl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2024.116167_bib1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.tips.2017.05.009","article-title":"Interstrand crosslink repair as a target for HDAC inhibition","volume":"38","author":"Nikolova","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2024.116167_bib2","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.trecan.2021.06.002","article-title":"Targeting the replication stress response through synthetic lethal strategies in cancer medicine","volume":"7","author":"Ngoi","year":"2021","journal-title":"Trends Cancer"},{"key":"10.1016\/j.ejmech.2024.116167_bib3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.trecan.2018.09.007","article-title":"Synthetically lethal interactions of ATM, ATR, and DNA-PKcs","volume":"4","author":"Kantidze","year":"2018","journal-title":"Trends Cancer"},{"key":"10.1016\/j.ejmech.2024.116167_bib4","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1002\/1878-0261.13224","article-title":"Resistance to DNA repair inhibitors in cancer","volume":"16","author":"Baxter","year":"2022","journal-title":"Mol. Oncol."},{"key":"10.1016\/j.ejmech.2024.116167_bib5","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41573-022-00558-5","article-title":"Targeting replication stress in cancer therapy","volume":"22","author":"da Costa","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2024.116167_bib6","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41568-018-0034-3","article-title":"Targeting ATR in cancer","volume":"18","author":"Lecona","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2024.116167_bib7","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nchembio.573","article-title":"Selective killing of ATM-or p53-deficient cancer cells through inhibition of ATR","volume":"7","author":"Reaper","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2024.116167_bib8","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1021\/jm101488z","article-title":"Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential Anticancer agents","volume":"54","author":"Charrier","year":"2011","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib9","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.4161\/cbt.21093","article-title":"The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy","volume":"13","author":"Prevo","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.ejmech.2024.116167_bib10","doi-asserted-by":"crossref","first-page":"6968","DOI":"10.1158\/0008-5472.CAN-13-3369","article-title":"ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by Disabling DNA replication initiation and fork elongation responses","volume":"74","author":"Joss\u00e9","year":"2014","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2024.116167_bib11","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1158\/0008-5472.CAN-13-0110","article-title":"ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status","volume":"73","author":"Huntoon","year":"2013","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2024.116167_bib12","doi-asserted-by":"crossref","first-page":"5547","DOI":"10.1021\/acs.jmedchem.9b00426","volume":"62","author":"Knegtel","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib13","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1200\/JCO.2017.76.6915","article-title":"Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors","volume":"36","author":"Thomas","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2024.116167_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107518","article-title":"Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): clinical candidate for cancer therapy","volume":"210","author":"Gorecki","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.ejmech.2024.116167_bib15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cbpa.2019.11.012","article-title":"Targeted protein degradation: current and future challenges","volume":"56","author":"Hanzl","year":"2020","journal-title":"Curr. Opin. Chem. Biol."},{"key":"10.1016\/j.ejmech.2024.116167_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.115037","article-title":"PROTACS: a technology with a gold rush-like atmosphere","volume":"247","author":"Wang","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1124\/pharmrev.122.000612","article-title":"Pharmacological modulation of the crosstalk between aberrant janus kinase signaling and epigenetic modifiers of the histone deacetylase family to treat cancer","volume":"75","author":"Mustafa","year":"2023","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ejmech.2024.116167_bib18","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/leu.2017.207","article-title":"BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells","volume":"32","author":"Sun","year":"2018","journal-title":"Leukemia"},{"key":"10.1016\/j.ejmech.2024.116167_bib19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.chembiol.2017.09.009","article-title":"The advantages of targeted protein degradation over inhibition: an RTK case study","volume":"25","author":"Burslem","year":"2018","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.ejmech.2024.116167_bib20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41392-022-00999-9","article-title":"PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)","volume":"7","author":"He","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"10.1016\/j.ejmech.2024.116167_bib21","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41571-023-00736-3","article-title":"Protein degraders enter the clinic\u2014a new approach to cancer therapy","volume":"20","author":"Chirnomas","year":"2023","journal-title":"Nature Rev. Clin. Oncol."},{"key":"10.1016\/j.ejmech.2024.116167_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13578-020-0376-x","article-title":"ATM, ATR and DNA-PKcs kinases\u2014the lessons from the mouse models: inhibition\u2260 deletion","volume":"10","author":"Menolfi","year":"2020","journal-title":"Cell Biosci."},{"key":"10.1016\/j.ejmech.2024.116167_bib23","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/j.jmb.2017.04.006","article-title":"Rationally designed PI3K\u03b1 mutants to mimic ATR and their use to understand binding specificity of ATR inhibitors","volume":"429","author":"Lu","year":"2017","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejmech.2024.116167_bib24","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/cr.2017.158","article-title":"Cryo-EM structure of human ATR-ATRIP complex","volume":"28","author":"Rao","year":"2018","journal-title":"Cell Res."},{"key":"10.1016\/j.ejmech.2024.116167_bib25","doi-asserted-by":"crossref","first-page":"7508","DOI":"10.1021\/jo00128a024","article-title":"Palladium (0)-catalyzed cross-coupling reaction of alkoxydiboron with haloarenes: a direct procedure for arylboronic esters","volume":"60","author":"Ishiyama","year":"1995","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib26","doi-asserted-by":"crossref","first-page":"29741","DOI":"10.1039\/D1RA05602F","article-title":"Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids","volume":"11","author":"Camacho","year":"2021","journal-title":"RSC Adv."},{"key":"10.1016\/j.ejmech.2024.116167_bib27","doi-asserted-by":"crossref","first-page":"6793","DOI":"10.1016\/j.bmcl.2011.09.035","article-title":"Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors","volume":"21","author":"Mortensen","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2024.116167_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112949","article-title":"PROTACs suppression of GSK-3\u03b2, a crucial kinase in neurodegenerative diseases","volume":"210","author":"Jiang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib29","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1021\/acs.jmedchem.6b01816","article-title":"Discovery of a small-molecule degrader of bromodomain and extra-terminal (BET) proteins with picomolar cellular potencies and capable of achieving tumor regression","volume":"61","author":"Zhou","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1021\/acs.jmedchem.8b00909","article-title":"Discovery of MD-224 as a first-in-class, highly potent, and efficacious proteolysis targeting chimera murine double minute 2 degrader capable of achieving complete and durable tumor regression","volume":"62","author":"Li","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib31","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1021\/acs.jmedchem.2c00324","article-title":"Structural feature analyzation strategies toward discovery of orally bioavailable PROTACs of Bruton's tyrosine kinase for the treatment of lymphoma","volume":"65","author":"Zhang","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib32","doi-asserted-by":"crossref","first-page":"26663","DOI":"10.1002\/anie.202108848","article-title":"Phenyl\u2010glutarimides: alternative cereblon binders for the design of PROTACs","volume":"60","author":"Min","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2024.116167_bib33","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1021\/acs.jmedchem.8b01631","article-title":"Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer","volume":"62","author":"Han","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2024.116167_bib34","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1476-5381.1965.tb02054.x","article-title":"The metabolism of thalidomide: the fate of thalidomide and some of its hydrolysis products in various species","volume":"25","author":"Schumacher","year":"1965","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"10.1016\/j.ejmech.2024.116167_bib35","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.3390\/cancers15143650","article-title":"NOXA accentuates apoptosis induction by a novel histone deacetylase inhibitor","volume":"15","author":"Ashry","year":"2023","journal-title":"Cancers"},{"key":"10.1016\/j.ejmech.2024.116167_bib36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Madhavi Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2024.116167_bib37","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: a software program for pKaprediction and protonation state generation for drug-like molecules","volume":"21","author":"Shelley","year":"2007","journal-title":"J. Comput. Aided Mol. Des."},{"key":"10.1016\/j.ejmech.2024.116167_bib38","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: improving force field accuracy on challenging regimes of chemical space","volume":"17","author":"Lu","year":"2021","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.ejmech.2024.116167_bib39","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/ci100015j","article-title":"ConfGen: a conformational search method for efficient generation of bioactive conformers","volume":"50","author":"Watts","year":"2010","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2024.116167_bib40","first-page":"1","article-title":"Comparative protein structure modeling using modeller","volume":"5","author":"Eramian","year":"2006","journal-title":"Current Protocols in Bioinformatics"},{"key":"10.1016\/j.ejmech.2024.116167_bib41","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1110\/ps.036061.108","article-title":"How well can the accuracy of comparative protein structure models be predicted?","volume":"17","author":"Eramian","year":"2008","journal-title":"Protein Sci."},{"key":"10.1016\/j.ejmech.2024.116167_bib42","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision Glide: docking and scoring incorporating a model of hydrophobic enclosure for Protein\u2212Ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424000473?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523424000473?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T14:17:39Z","timestamp":1735049859000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523424000473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":42,"alternative-id":["S0223523424000473"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.116167","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv-2023-szkt8-v2","asserted-by":"object"},{"id-type":"doi","id":"10.26434\/chemrxiv-2023-szkt8","asserted-by":"object"}]},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis, and biological characterization of proteolysis targeting chimera (PROTACs) for the ataxia telangiectasia and RAD3-related (ATR) kinase","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2024.116167","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Author(s). Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"116167"}}