{"doi":"10.1023/b:drug.0000006171.54078.3d","title":"The Antiangiogenic Agent Neovastat (Æ-941) Stimulates Tissue Plasminogen Activator Activity","abstract":null,"journal":"Investigational New Drugs","year":2004,"id":639159,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1660484,"name":"Dominique Labelle","orcid":null,"position":1,"is_corresponding":false},{"id":1660485,"name":"Carine Nyalendo","orcid":null,"position":2,"is_corresponding":false},{"id":1660486,"name":"Dominique Boivin","orcid":null,"position":3,"is_corresponding":false},{"id":1660487,"name":"Michel Demeule","orcid":null,"position":4,"is_corresponding":false},{"id":1660488,"name":"Chantal Barthomeuf","orcid":null,"position":5,"is_corresponding":false},{"id":1660489,"name":"Richard Béliveau","orcid":null,"position":6,"is_corresponding":false},{"id":1660483,"name":"Denis Gingras","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Antiangiogenic Agent Neovastat (Æ-941) Stimulates Tissue Plasminogen Activator Activity","abstract":"The plasminogen activator/plasmin system represents a key component of the proteolytic machinery underlying angiogenesis. In this work, we investigated the effect of Neovastat (AE-941), a naturally occurring multifunctional antiangiogenic agent that is currently in Phase III clinical trials, on tissue and urokinase plasminogen activator activities. We found that in vitro, Neovastat at 100 microg/ml markedly stimulates t-PA-mediated plasmin generation, while it slightly inhibits the generation of plasmin mediated by uPA. The stimulatory effect of Neovastat on t-PA activity was markedly increased by a heat treatment, resulting in a 15-fold increase in the rate of activation of plasminogen. Neovastat did not directly stimulate the activity of t-PA or plasmin towards exogenous substrates, suggesting that its effect requires the presence of plasminogen. Accordingly, kinetic analysis showed that Neovastat increases both the k(cat) of t-PA as well as its affinity for plasminogen by 10-fold. The stimulation of t-PA activity by Neovastat was also correlated with a direct interaction of Neovastat with plasminogen as monitored by the surface plasmon resonance technology. Overall, these results identify Neovastat as a potent stimulator of t-PA-dependent activation of plasminogen, further emphasizing its pleiotropic mechanism of action on several molecular events involved in angiogenesis.","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"14707491","pmcid":null,"openalex_id":"https://openalex.org/W1984395407","authors":[],"funders":[{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"}],"total_grants":1,"fwci":1.2583,"citation_percentile":0.78086357,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":2}],"oa_status":"closed","license":"Springer Nature TDM","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1023/B:DRUG.0000006171.54078.3d.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1023/B:DRUG.0000006171.54078.3d/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1023/b:drug.0000006171.54078.3d","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14707491","host_type":"repository"},{"url":"https://dx.doi.org/10.1023/b:drug.0000006171.54078.3d","host_type":""}],"fields_of_study":["Protease and Inhibitor Mechanisms","Angiogenesis and VEGF in Cancer","Blood Coagulation and Thrombosis Mechanisms","0301 basic medicine","03 medical and health sciences","0302 clinical medicine","Angiogenesis Inhibitors","Catalysis","Fibrinolysin","Hot Temperature","Plasminogen","Tissue Extracts","Tissue Plasminogen Activator","Urokinase-Type Plasminogen Activator"],"mesh_terms":["Catalysis","Fibrinolysin","Hot Temperature","Plasminogen","Tissue Plasminogen Activator","Tissue Extracts","Urokinase-Type Plasminogen Activator","Angiogenesis Inhibitors"],"keywords":["Plasmin","Plasminogen activator","Urokinase","Angiogenesis","Tissue plasminogen activator","Chemistry","In vitro","Stimulation","T-plasminogen activator","Fibrinolysis","Activator (genetics)","Pharmacology","Biochemistry","Enzyme","Biology","Receptor","Endocrinology","Cancer research","Internal medicine","Medicine","Hot Temperature","Tissue Extracts","Angiogenesis Inhibitors","Plasminogen","Fibrinolysin","Urokinase-Type Plasminogen Activator","Catalysis"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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