{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ding Y"],"funding":["Duncan Family Institute for Cancer Prevention and Risk Assessment","NIDA NIH HHS","U.S. Department of Defense","National Cancer Institute","NCI NIH HHS","University of Texas MD Anderson Cancer Center","National Institute on Drug Abuse","Sanofi"],"pagination":["2737-2752"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6388690"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["61(7)"],"pubmed_abstract":["Covalent drug discovery has undergone a resurgence in recent years due to comprehensive optimization of the structure-activity relationship (SAR) and the structure-reactivity relationship (SRR) for covalent drug candidates. The natural product oridonin maintains an impressive pharmacological profile through its covalent enone warhead on the D-ring and has attracted substantial SAR studies to characterize its potential in the development of new molecular entities for the treatment of various human cancers and inflammation. Herein, for the first time, we report the excessive reactivity of this covalent warhead and mediation of the covalent binding capability through a Rh2(esp)2-catalyzed mild and concise regio- and stereospecific aziridination approach. Importantly, aziridonin 44 (YD0514), w"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Regio- and Stereospecific Synthesis of Oridonin D-Ring Aziridinated Analogues for the Treatment of Triple-Negative Breast Cancer via Mediated Irreversible Covalent Warheads."],"pmcid":["PMC6388690"],"funding_grant_id":["R01 DA038446","P30 CA016672","BC160038","BC160038P1","F31 DA045511","T32 DA007287","P30 DA028821"],"pubmed_authors":["Liu Z","Ding Y","Wang P","Ye N","Shen Q","Li D","Ding C","White MA","Wold EA","Chen H","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"Regio- and Stereospecific Synthesis of Oridonin D-Ring Aziridinated Analogues for the Treatment of Triple-Negative Breast Cancer via Mediated Irreversible Covalent Warheads.","description":"Covalent drug discovery has undergone a resurgence in recent years due to comprehensive optimization of the structure-activity relationship (SAR) and the structure-reactivity relationship (SRR) for covalent drug candidates. The natural product oridonin maintains an impressive pharmacological profile through its covalent enone warhead on the D-ring and has attracted substantial SAR studies to characterize its potential in the development of new molecular entities for the treatment of various human cancers and inflammation. Herein, for the first time, we report the excessive reactivity of this covalent warhead and mediation of the covalent binding capability through a Rh2(esp)2-catalyzed mild and concise regio- and stereospecific aziridination approach. Importantly, aziridonin 44 (YD0514), w","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Apr","modification":"2025-04-18T14:07:59.283Z","creation":"2019-08-03T07:21:37Z"},"accession":"S-EPMC6388690","cross_references":{"pubmed":["29528645"],"doi":["10.1021/acs.jmedchem.7b01514"]}}