{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:30:08Z","timestamp":1790235008061,"version":"4.1.0"},"reference-count":46,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,3,27]]},"abstract":"<jats:title>Key Points<\/jats:title><jats:p>VKORC1 is more sensitive than VKORC1L1 to OAC inhibition, whereby 4-hydroxycoumarin rodenticides are equally effective. In silico and in vitro analysis revealed OAC binding sites that are different for VKORC1 and VKORC1L1.<\/jats:p>","DOI":"10.1182\/bloodadvances.2017006775","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T16:00:10Z","timestamp":1522080010000},"page":"691-702","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":23,"title":["VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites"],"prefix":"10.1182","volume":"2","author":[{"given":"Katrin J.","family":"Czogalla","sequence":"first","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Liphardt","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"H\u00f6ning","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University Clinic Bonn, Bonn, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veit","family":"Hornung","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, University Clinic Bonn, Bonn, Germany;"},{"name":"Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arijit","family":"Biswas","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Watzka","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine and"},{"name":"Center for Rare Diseases Bonn, University Clinic Bonn; Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Institute of Experimental Haematology and Transfusion Medicine and"},{"name":"Center for Rare Diseases Bonn, University Clinic Bonn; Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"issue":"1","key":"2019111619322913200_B1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1161\/01.CIR.19.1.97","article-title":"The discovery of dicumarol and its sequels","volume":"19","author":"Link","year":"1959","journal-title":"Circulation"},{"issue":"153","key":"2019111619322913200_B2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0021-9258(18)51207-2","article-title":"Studies on the hemorrhagic sweet clover disease: XIII. Anticoagulant activity and structure in the 4-hydroxycoumarin group","author":"Overman","year":"1944","journal-title":"J Biol Chem"},{"issue":"12","key":"2019111619322913200_B3","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2165\/00003088-200544120-00003","article-title":"Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol","volume":"44","author":"Ufer","year":"2005","journal-title":"Clin Pharmacokinet"},{"issue":"7","key":"2019111619322913200_B4","first-page":"517","article-title":"Recommendations on bleeding and nonbleeding complications of vitamin K antagonists","volume":"5","author":"Ansell","year":"2007","journal-title":"Clin Adv Hematol Oncol"},{"issue":"3","key":"2019111619322913200_B5","first-page":"570","article-title":"Current pharmacogenetic developments in oral anticoagulation therapy: the influence of variant VKORC1 and CYP2C9 alleles","volume":"98","author":"Oldenburg","year":"2007","journal-title":"Thromb Haemost"},{"issue":"6974","key":"2019111619322913200_B6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nature02214","article-title":"Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2","volume":"427","author":"Rost","year":"2004","journal-title":"Nature"},{"issue":"51","key":"2019111619322913200_B7","doi-asserted-by":"crossref","first-page":"19308","DOI":"10.1073\/pnas.0609401103","article-title":"Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2","volume":"103","author":"Chu","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6974","key":"2019111619322913200_B8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nature02254","article-title":"Identification of the gene for vitamin K epoxide reductase","volume":"427","author":"Li","year":"2004","journal-title":"Nature"},{"issue":"3","key":"2019111619322913200_B9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1194\/jlr.R045559","article-title":"Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis","volume":"55","author":"Shearer","year":"2014","journal-title":"J Lipid Res"},{"issue":"9","key":"2019111619322913200_B10","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1182\/blood.V75.9.1753.1753","article-title":"Molecular basis of vitamin K-dependent gamma-carboxylation","volume":"75","author":"Furie","year":"1990","journal-title":"Blood"},{"issue":"12","key":"2019111619322913200_B11","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1111\/j.1538-7836.2004.00968.x","article-title":"The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis","volume":"2","author":"Berkner","year":"2004","journal-title":"J Thromb Haemost"},{"issue":"8","key":"2019111619322913200_B12","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.3390\/nu7085280","article-title":"VKORC1 and VKORC1L1: why do vertebrates have two vitamin K 2,3-epoxide reductases?","volume":"7","author":"Oldenburg","year":"2015","journal-title":"Nutrients"},{"issue":"13","key":"2019111619322913200_B13","doi-asserted-by":"crossref","first-page":"9396","DOI":"10.1074\/jbc.M113.534446","article-title":"Conserved loop cysteines of vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) are involved in its active site regeneration","volume":"289","author":"Tie","year":"2014","journal-title":"J Biol Chem"},{"issue":"17","key":"2019111619322913200_B14","doi-asserted-by":"crossref","first-page":"15085","DOI":"10.1074\/jbc.M110.210971","article-title":"Human vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1) mediates vitamin K-dependent intracellular antioxidant function","volume":"286","author":"Westhofen","year":"2011","journal-title":"J Biol Chem"},{"issue":"6","key":"2019111619322913200_B15","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1160\/TH09-03-0204","article-title":"VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding","volume":"101","author":"Spohn","year":"2009","journal-title":"Thromb Haemost"},{"issue":"4","key":"2019111619322913200_B16","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3109\/10409238.2013.791659","article-title":"Structural and functional insights into human vitamin K epoxide reductase and vitamin K epoxide reductase-like1","volume":"48","author":"Van Horn","year":"2013","journal-title":"Crit Rev Biochem Mol Biol"},{"issue":"40","key":"2019111619322913200_B17","doi-asserted-by":"crossref","first-page":"28733","DOI":"10.1074\/jbc.M113.457119","article-title":"VKORC1L1, an enzyme rescuing the vitamin K 2,3-epoxide reductase activity in some extrahepatic tissues during anticoagulation therapy","volume":"288","author":"Hammed","year":"2013","journal-title":"J Biol Chem"},{"issue":"5","key":"2019111619322913200_B18","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.thromres.2015.01.025","article-title":"Two enzymes catalyze vitamin K 2,3-epoxide reductase activity in mouse: VKORC1 is highly expressed in exocrine tissues while VKORC1L1 is highly expressed in brain","volume":"135","author":"Caspers","year":"2015","journal-title":"Thromb Res"},{"issue":"6096","key":"2019111619322913200_B19","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"issue":"1","key":"2019111619322913200_B20","doi-asserted-by":"crossref","first-page":"14987","DOI":"10.1038\/srep14987","article-title":"Synthesis of an arrayed sgRNA library targeting the human genome","volume":"5","author":"Schmidt","year":"2015","journal-title":"Sci Rep"},{"issue":"10","key":"2019111619322913200_B21","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1101\/gr.176701.114","article-title":"OutKnocker: a web tool for rapid and simple genotyping of designer nuclease edited cell lines","volume":"24","author":"Schmid-Burgk","year":"2014","journal-title":"Genome Res"},{"issue":"7","key":"2019111619322913200_B22","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1093\/nar\/gkv226","article-title":"Advances in CRISPR-Cas9 genome engineering: lessons learned from RNA interference","volume":"43","author":"Barrangou","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2019111619322913200_B23","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jsb.2010.06.016","article-title":"Applications of the Restriction Free (RF) cloning procedure for molecular manipulations and protein expression","volume":"172","author":"Unger","year":"2010","journal-title":"J Struct Biol"},{"issue":"15","key":"2019111619322913200_B24","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1182\/blood-2013-05-501692","article-title":"Human VKORC1 mutations cause variable degrees of 4-hydroxycoumarin resistance and affect putative warfarin binding interfaces","volume":"122","author":"Czogalla","year":"2013","journal-title":"Blood"},{"issue":"7280","key":"2019111619322913200_B25","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature08720","article-title":"Structure of a bacterial homologue of vitamin K epoxide reductase","volume":"463","author":"Li","year":"2010","journal-title":"Nature"},{"issue":"4","key":"2019111619322913200_B26","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: a unified platform for automated protein structure and function prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat Protoc"},{"issue":"20","key":"2019111619322913200_B27","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","article-title":"YASARA View: molecular graphics for all devices: from smartphones to workstations","volume":"30","author":"Krieger","year":"2014","journal-title":"Bioinformatics"},{"issue":"13","key":"2019111619322913200_B28","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera: a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"issue":"14","key":"2019111619322913200_B29","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"19","author":"Morris","year":"1998","journal-title":"J Comput Chem"},{"issue":"1","key":"2019111619322913200_B30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nsmb.3338","article-title":"Warfarin and vitamin K compete for binding to Phe55 in human VKOR","volume":"24","author":"Czogalla","year":"2017","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"2019111619322913200_B31","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nsmb.3333","article-title":"Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer","volume":"24","author":"Shen","year":"2017","journal-title":"Nat Struct Mol Biol"},{"issue":"6","key":"2019111619322913200_B32","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1016\/j.bmc.2007.01.014","article-title":"Synthesis and structure-activity relationships of novel warfarin derivatives","volume":"15","author":"Gebauer","year":"2007","journal-title":"Bioorg Med Chem"},{"issue":"8","key":"2019111619322913200_B33","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1016\/j.bbagen.2013.04.018","article-title":"Determination of the warfarin inhibition constant Ki for vitamin K 2,3-epoxide reductase complex subunit-1 (VKORC1) using an in vitro DTT-driven assay","volume":"1830","author":"Bevans","year":"2013","journal-title":"Biochim Biophys Acta"},{"issue":"10","key":"2019111619322913200_B34","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1182\/blood-2010-08-304303","article-title":"Functional study of the vitamin K cycle in mammalian cells","volume":"117","author":"Tie","year":"2011","journal-title":"Blood"},{"issue":"8","key":"2019111619322913200_B35","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1111\/jth.12306","article-title":"Evaluation of warfarin resistance using transcription activator-like effector nucleases-mediated vitamin K epoxide reductase knockout HEK293 cells","volume":"11","author":"Tie","year":"2013","journal-title":"J Thromb Haemost"},{"issue":"5","key":"2019111619322913200_B36","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/jth.12185","article-title":"A new cell culture-based assay quantifies vitamin K 2,3-epoxide reductase complex subunit 1 function and reveals warfarin resistance phenotypes not shown by the dithiothreitol-driven VKOR assay","volume":"11","author":"Fregin","year":"2013","journal-title":"J Thromb Haemost"},{"issue":"4","key":"2019111619322913200_B37","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1182\/blood-2013-05-505123","article-title":"A cellular system for quantitation of vitamin K cycle activity: structure-activity effects on vitamin K antagonism by warfarin metabolites","volume":"123","author":"Haque","year":"2014","journal-title":"Blood"},{"issue":"17","key":"2019111619322913200_B38","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1021\/bi051986y","article-title":"r-VKORC1 expression in factor IX BHK cells increases the extent of factor IX carboxylation but is limited by saturation of another carboxylation component or by a shift in the rate-limiting step","volume":"45","author":"Hallgren","year":"2006","journal-title":"Biochemistry"},{"issue":"6","key":"2019111619322913200_B39","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1365-2141.2008.07119.x","article-title":"The story of the discovery of heparin and warfarin","volume":"141","author":"Wardrop","year":"2008","journal-title":"Br J Haematol"},{"issue":"1","key":"2019111619322913200_B40","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/path.1700130121","article-title":"The histology of liver tissue regeneration","volume":"13","author":"Milne","year":"1909","journal-title":"J Pathol"},{"issue":"6","key":"2019111619322913200_B41","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.201409111","article-title":"GGCX and VKORC1 inhibit osteocalcin endocrine functions","volume":"208","author":"Ferron","year":"2015","journal-title":"J Cell Biol"},{"issue":"4","key":"2019111619322913200_B42","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.tmrv.2015.06.002","article-title":"Long-acting anticoagulant rodenticide (superwarfarin) poisoning: a review of its historical development, epidemiology, and clinical management","volume":"29","author":"King","year":"2015","journal-title":"Transfus Med Rev"},{"key":"2019111619322913200_B43","unstructured":"Hadler MR , BuckleAP. Forty-five years of anticoagulant rodenticides: past, present and future trends. In: Borrecco JE, Marsh RE, eds. Proceedings of the Fifteenth Vertebrate Pest Conference. Davis, CA, University of California, Davis; 1992:149-155."},{"key":"2019111619322913200_B44","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.phytochem.2015.08.012","article-title":"Comparative inhibitory effect of prenylated coumarins, ferulenol and ferprenin, contained in the \u2018poisonous chemotype\u2019 of Ferula communis on mammal liver microsomal VKORC1 activity","volume":"118","author":"Louvet","year":"2015","journal-title":"Phytochemistry"},{"issue":"16","key":"2019111619322913200_B45","doi-asserted-by":"crossref","first-page":"16410","DOI":"10.1074\/jbc.M500765200","article-title":"Membrane topology mapping of vitamin K epoxide reductase by in vitro translation\/cotranslocation","volume":"280","author":"Tie","year":"2005","journal-title":"J Biol Chem"},{"issue":"8","key":"2019111619322913200_B46","doi-asserted-by":"crossref","first-page":"6837","DOI":"10.3390\/nu7085313","article-title":"Structural modeling insights into human VKORC1 phenotypes","volume":"7","author":"Czogalla","year":"2015","journal-title":"Nutrients"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/6\/691\/882980\/advances006775.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/2\/6\/691\/882980\/advances006775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T01:01:52Z","timestamp":1660698112000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/2\/6\/691\/15814\/VKORC1-and-VKORC1L1-have-distinctly-different-oral"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,26]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,3,27]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2017006775","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,26]]}}}