{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Calbert ML"],"funding":["Alex's Lemonade Stand Foundation for Childhood Cancer","French Infrastructure for Integrated Structural Biology","National Cancer Institute","NCI NIH HHS"],"pagination":["683-699"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11286238"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(5)"],"pubmed_abstract":["Anticancer nucleosides are effective against solid tumors and hematologic malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4'-ethynyl-2'-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induces replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å cocrystal structure of DCK bound to EdC and UDP reveals how the rigid 4'-alkyne of EdC fits within the active site of DCK. Remarkably, EdC was resistant to"],"journal":["Molecular cancer therapeutics"],"pubmed_title":["4'-Ethynyl-2'-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress."],"pmcid":["PMC11286238"],"funding_grant_id":["K22 CA251649","R01 CA279364","P30 CA010815","P30 CA056036","2022 A Award","K22CA251649","R01CA279364","ANR-10-INSB-05-01","R01 CA214799","R01 CA236853","R01CA236853"],"pubmed_authors":["Childers WE","Betzi S","Rees MG","Johnson N","Gordon J","Kent T","Grana X","Toma MM","Ronan MM","Pomerantz RT","Wang Y","Roth JA","Mitra R","Boghossian AS","Gorman N","Saez-Ayala M","Tyagi M","Hurtz C","Eischen CM","Chandramouly G","Adams CM","Morelli X","Calbert ML","Atkins J","Goldman AR","Skorski T","Ayyadevara VSSA","Krais JJ"],"additional_accession":[]},"is_claimable":false,"name":"4'-Ethynyl-2'-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress.","description":"Anticancer nucleosides are effective against solid tumors and hematologic malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4'-ethynyl-2'-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induces replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å cocrystal structure of DCK bound to EdC and UDP reveals how the rigid 4'-alkyne of EdC fits within the active site of DCK. Remarkably, EdC was resistant to","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2025-04-04T00:29:09.698Z","creation":"2025-04-04T00:29:09.698Z"},"accession":"S-EPMC11286238","cross_references":{"pubmed":["38064712"],"doi":["10.1158/1535-7163.MCT-23-0487","10.1158/1535-7163.mct-23-0487"]}}