{"id":"https://openalex.org/W2005184538","doi":"https://doi.org/10.1055/s-2007-996127","title":"Enzyme-Controlling Medicines: Introduction","display_name":"Enzyme-Controlling Medicines: Introduction","publication_year":1997,"publication_date":"1997-12-01","ids":{"openalex":"https://openalex.org/W2005184538","doi":"https://doi.org/10.1055/s-2007-996127","mag":"2005184538","pmid":"https://pubmed.ncbi.nlm.nih.gov/9469621"},"language":"en","primary_location":{"id":"doi:10.1055/s-2007-996127","doi":"https://doi.org/10.1055/s-2007-996127","is_oa":false,"landing_page_url":"https://doi.org/10.1055/s-2007-996127","pdf_url":null,"source":{"id":"https://openalex.org/S96726197","display_name":"Seminars in Thrombosis and Hemostasis","issn_l":"0094-6176","issn":["0094-6176","1098-9064"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320000","host_organization_name":"Thieme Medical Publishers (Germany)","host_organization_lineage":["https://openalex.org/P4310320000"],"host_organization_lineage_names":["Thieme Medical Publishers (Germany)"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Seminars in Thrombosis and Hemostasis","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111751626","display_name":"Shosuke Okamoto","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shosuke Okamoto","raw_affiliation_strings":["Kobe Research Projects on Thrombosis and Haemostasis, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Kobe Research Projects on Thrombosis and Haemostasis, Japan","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069093775","display_name":"Akiko Hijikata\u2010Okunomiya","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Akiko Hijikata-Okunomiya","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5021607990","display_name":"Keiko Wanaka","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Keiko Wanaka","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5105466143","display_name":"Yoshio Okada","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yoshio Okada","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5087054701","display_name":"Utako OKAMOTO","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Utako Okamoto","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":123,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":97,"max":99},"biblio":{"volume":"23","issue":"06","first_page":"493","last_page":"501"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.9824000000953674,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10881","display_name":"Blood Coagulation and Thrombosis Mechanisms","score":0.9824000000953674,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11917","display_name":"Coagulation, Bradykinin, Polyphosphates, and Angioedema","score":0.006200000178068876,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10620","display_name":"Protease and Inhibitor Mechanisms","score":0.002899999963119626,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/enzyme-inhibitors","display_name":"enzyme inhibitors","score":0.75},{"id":"https://openalex.org/keywords/fibrinolysis","display_name":"fibrinolysis","score":0.843999981880188},{"id":"https://openalex.org/keywords/plasmin-inhibitor","display_name":"plasmin inhibitor","score":0.9700000286102295},{"id":"https://openalex.org/keywords/epsilon-aminocaproic-acid","display_name":"epsilon-aminocaproic acid","score":0.8830000162124634},{"id":"https://openalex.org/keywords/tranexamic-acid","display_name":"tranexamic acid","score":0.9990000128746033},{"id":"https://openalex.org/keywords/thrombin-inhibitors","display_name":"thrombin inhibitors","score":0.8769999742507935},{"id":"https://openalex.org/keywords/argatroban","display_name":"argatroban","score":0.9660000205039978},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.7720000147819519},{"id":"https://openalex.org/keywords/lysine-derivatives","display_name":"lysine derivatives","score":0.7490000128746033},{"id":"https://openalex.org/keywords/kallikrein-inhibitor","display_name":"kallikrein inhibitor","score":0.871999979019165},{"id":"https://openalex.org/keywords/competitive-inhibition","display_name":"competitive inhibition","score":0.6159999966621399},{"id":"https://openalex.org/keywords/thrombosis-treatment","display_name":"thrombosis treatment","score":0.7829999923706055}],"concepts":[{"id":"https://openalex.org/C2781071845","wikidata":"https://www.wikidata.org/wiki/Q21173374","display_name":"Plasmin","level":3,"score":0.8075778484344482},{"id":"https://openalex.org/C2779637338","wikidata":"https://www.wikidata.org/wiki/Q418666","display_name":"Tranexamic acid","level":3,"score":0.7181288003921509},{"id":"https://openalex.org/C2776825266","wikidata":"https://www.wikidata.org/wiki/Q1410794","display_name":"Fibrinolysis","level":2,"score":0.6966780424118042},{"id":"https://openalex.org/C2777278314","wikidata":"https://www.wikidata.org/wiki/Q255968","display_name":"Aminocaproic acid","level":2,"score":0.5755069255828857},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5369963049888611},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.4684940278530121},{"id":"https://openalex.org/C2776016237","wikidata":"https://www.wikidata.org/wiki/Q178430","display_name":"Lysine","level":3,"score":0.4626271426677704},{"id":"https://openalex.org/C2781436528","wikidata":"https://www.wikidata.org/wiki/Q575222","display_name":"Antifibrinolytic","level":4,"score":0.4340306520462036},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4102882742881775},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.4015895128250122},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.34228163957595825},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.270668625831604},{"id":"https://openalex.org/C141071460","wikidata":"https://www.wikidata.org/wiki/Q40821","display_name":"Surgery","level":1,"score":0.2682439386844635},{"id":"https://openalex.org/C515207424","wikidata":"https://www.wikidata.org/wiki/Q8066","display_name":"Amino acid","level":2,"score":0.09768635034561157},{"id":"https://openalex.org/C2991743468","wikidata":"https://www.wikidata.org/wiki/Q166019","display_name":"Blood loss","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000933","descriptor_name":"Antifibrinolytic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D000991","descriptor_name":"Antithrombins","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":false},{"descriptor_ui":"D000991","descriptor_name":"Antithrombins","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D001120","descriptor_name":"Arginine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007610","descriptor_name":"Kallikreins","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D010649","descriptor_name":"Phenylalanine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D010649","descriptor_name":"Phenylalanine","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D010875","descriptor_name":"Pipecolic Acids","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":false},{"descriptor_ui":"D010875","descriptor_name":"Pipecolic Acids","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D013449","descriptor_name":"Sulfonamides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014148","descriptor_name":"Tranexamic Acid","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D015119","descriptor_name":"Aminocaproic Acid","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1055/s-2007-996127","doi":"https://doi.org/10.1055/s-2007-996127","is_oa":false,"landing_page_url":"https://doi.org/10.1055/s-2007-996127","pdf_url":null,"source":{"id":"https://openalex.org/S96726197","display_name":"Seminars in Thrombosis and Hemostasis","issn_l":"0094-6176","issn":["0094-6176","1098-9064"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320000","host_organization_name":"Thieme Medical Publishers (Germany)","host_organization_lineage":["https://openalex.org/P4310320000"],"host_organization_lineage_names":["Thieme Medical Publishers (Germany)"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Seminars in Thrombosis and Hemostasis","raw_type":"journal-article"},{"id":"pmid:9469621","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/9469621","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Seminars in thrombosis and hemostasis","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.8371999859809875,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1978261092","https://openalex.org/W2991786765","https://openalex.org/W2029863503","https://openalex.org/W2055420530","https://openalex.org/W1150150594","https://openalex.org/W2003341676","https://openalex.org/W617709438","https://openalex.org/W2016642690","https://openalex.org/W1966777422","https://openalex.org/W1990724209"],"abstract_inverted_index":{"A":[0],"short":[1],"history":[2],"of":[3,7,27,43,87,124,127,141,156],"the":[4,13,21,24,41,62,68,80,85,88,101,125],"research":[5],"work":[6],"S.":[8],"Okamoto":[9],"and":[10,51,57,96,152],"co-workers,":[11],"for":[12,37,131],"previous":[14,146],"50":[15],"years,":[16],"is":[17,129],"briefly":[18],"described.":[19],"In":[20,61],"1950s,":[22],"when":[23],"physiologic":[25],"role":[26],"fibrinolysis":[28],"had":[29],"not":[30],"been":[31,159],"established,":[32],"they":[33],"began":[34],"to":[35,71,84,99,105],"seek":[36],"compounds":[38],"that":[39],"inhibit":[40],"action":[42,126],"plasmin.":[44],"They":[45],"examined":[46],"approximately":[47],"200":[48],"lysine":[49],"derivatives":[50],"discovered":[52],"epsilon":[53],"aminocaproic":[54],"acid":[55,59],"(EACA)":[56],"tranexamic":[58],"(t-AMCHA).":[60],"1970s,":[63],"we":[64],"selected":[65],"thrombin":[66,90,119],"as":[67,79],"target":[69],"enzyme":[70],"be":[72],"controlled;":[73],"structure-activity":[74],"relationship":[75],"studies,":[76,147],"taking":[77,139],"arginine":[78],"skeleton":[81],"structure,":[82],"led":[83,104],"discovery":[86],"selective":[89,154],"inhibitor":[91,155],"No.":[92,106],"205":[93],"(4-ethyl-1-[N2-(5-dimethylamino-1-naphthalenesulfonyl)-L-arginyl]-":[94],"1-piperidine),":[95],"further":[97],"attempts":[98],"minimize":[100],"toxicity":[102],"finally":[103],"805":[107],"(argatroban,":[108],"MD-805,":[109],"(2R,4R)-4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)-sulfo":[110],"nyl]-L-arginyl)-2-piperidine":[111],"carboxylic":[112],"acid).":[113],"Argatroban,":[114],"without":[115],"any":[116],"cofactor,":[117],"inhibits":[118],"competitively.":[120],"The":[121],"high":[122],"selectivity":[123],"argatroban":[128],"promising":[130],"treating":[132],"thrombosis":[133],"in":[134],"clinical":[135],"practice.":[136],"More":[137],"recently,":[138],"advantage":[140],"our":[142],"knowledge":[143],"obtained":[144],"through":[145],"active":[148],"center-directed":[149],"plasmin":[150],"inhibitors":[151],"a":[153],"kallikrein":[157],"have":[158],"found.":[160]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":12},{"year":2023,"cited_by_count":9},{"year":2022,"cited_by_count":5},{"year":2021,"cited_by_count":8},{"year":2020,"cited_by_count":10},{"year":2019,"cited_by_count":10},{"year":2018,"cited_by_count":4},{"year":2017,"cited_by_count":9},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":4},{"year":2014,"cited_by_count":6},{"year":2013,"cited_by_count":11},{"year":2012,"cited_by_count":6}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
