{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:52:52Z","timestamp":1777960372617,"version":"3.51.4"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,4,12]],"date-time":"2013-04-12T00:00:00Z","timestamp":1365724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"Background and Purpose<\/jats:title>Ectonucleotidases control extracellular nucleotide levels and consequently, their (patho)physiological responses. Among these enzymes, nucleoside triphosphate diphosphohydrolase\u20101 (NTPD<\/jats:styled-content>ase1), \u22122, \u22123 and \u22128 are the major ectonucleotidases responsible for nucleotide hydrolysis at the cell surface under physiological conditions, and NTPDa<\/jats:styled-content>se1 is predominantly located at the surface of vascular endothelial cells and leukocytes. Efficacious inhibitors of NTPD<\/jats:styled-content>ase1 are required to modulate responses induced by nucleotides in a number of pathological situations such as thrombosis, inflammation and cancer.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>Here, we present the synthesis and enzymatic characterization of five 8\u2010BuS<\/jats:styled-content>\u2010adenine nucleotide derivatives as potent and selective inhibitors of NTPD<\/jats:styled-content>ase1.<\/jats:p><\/jats:sec>Key Results<\/jats:title>The compounds 8\u2010BuS<\/jats:styled-content>\u2010AMP<\/jats:styled-content>, 8\u2010BuS<\/jats:styled-content>\u2010ADP<\/jats:styled-content> and 8\u2010BuS<\/jats:styled-content>\u2010ATP<\/jats:styled-content> inhibit recombinant human and mouse NTPD<\/jats:styled-content>ase1 by mixed type inhibition, predominantly competitive with K<\/jats:styled-content><\/jats:italic>i<\/jats:sub><\/jats:styled-content> values <1\u2009\u03bcM<\/jats:styled-content>. In contrast to 8\u2010BuS<\/jats:styled-content>\u2010ATP<\/jats:styled-content> which could be hydrolyzed by other NTPD<\/jats:styled-content>ases, the other BuS<\/jats:styled-content> derivatives were resistant to hydrolysis by either NTPD<\/jats:styled-content>ase1, \u22122, \u22123 or \u22128. 8\u2010BuS<\/jats:styled-content>\u2010AMP<\/jats:styled-content> and 8\u2010BuS<\/jats:styled-content>\u2010ADP<\/jats:styled-content> were the most potent and selective inhibitors of NTPD<\/jats:styled-content>ase1 expressed in human umbilical vein endothelial cells as well as in situ<\/jats:italic> in human and mouse tissues. As expected, as a result of their inhibition of recombinant human NTPD<\/jats:styled-content>ase1, 8\u2010BuS<\/jats:styled-content>\u2010AMP<\/jats:styled-content> and 8\u2010BuS<\/jats:styled-content>\u2010ADP<\/jats:styled-content> impaired the ability of this enzyme to block platelet aggregation. Importantly, neither of these two inhibitors triggered platelet aggregation nor prevented ADP<\/jats:styled-content>\u2010induced platelet aggregation, in support of their inactivity towards P2Y<\/jats:styled-content>1<\/jats:sub><\/jats:styled-content> and P2Y<\/jats:styled-content>12<\/jats:sub><\/jats:styled-content> receptors.<\/jats:p><\/jats:sec>Conclusions and Implications<\/jats:title>The 8\u2010BuS<\/jats:styled-content>\u2010AMP<\/jats:styled-content> and 8\u2010BuS<\/jats:styled-content>\u2010ADP<\/jats:styled-content> have therefore potential to serve as drugs for the treatment of pathologies regulated by NTPD<\/jats:styled-content>ase1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12135","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T12:58:12Z","timestamp":1361365092000},"page":"179-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["8\u2010BuS<\/scp>\u2010ATP<\/scp> derivatives as specific NTPD<\/scp>ase1 inhibitors"],"prefix":"10.1111","volume":"169","author":[{"given":"Joanna","family":"Lecka","sequence":"first","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Gillerman","sequence":"additional","affiliation":[{"name":"Department of Chemistry Bar\u2010Ilan University Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Fausther","sequence":"additional","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabrouka","family":"Salem","sequence":"additional","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes N","family":"Munkonda","sequence":"additional","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Philippe","family":"Brosseau","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences Universit\u00e9 de Sherbrooke Sherbrooke QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Cadot","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Endocrinology and Genomic Unit Centre de recherche du CHU de Qu\u00e9bec and Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireia","family":"Mart\u00edn\u2010Satu\u00e9","sequence":"additional","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"},{"name":"Department of Pathology and Experimental Therapeutics University of Barcelona Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"d'Orl\u00e9ans\u2010Juste","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medicine and Health Sciences Universit\u00e9 de Sherbrooke Sherbrooke QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c9ric","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences Universit\u00e9 de Sherbrooke Sherbrooke QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Poirier","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry, Endocrinology and Genomic Unit Centre de recherche du CHU de Qu\u00e9bec and Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beat","family":"K\u00fcnzli","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bilha","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Chemistry Bar\u2010Ilan University Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"S\u00e9vigny","sequence":"additional","affiliation":[{"name":"Centre de recherche en Rhumatologie et Immunologie Centre Hospitalier Universitaire (CHU) de Qu\u00e9bec and D\u00e9partement de microbiologie\u2010infectiologie et d'immunologie Facult\u00e9 de m\u00e9decine Universit\u00e9 Laval Qu\u00e9bec QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2005.12.025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9003297"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(88)90484-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.tb20068.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0362222"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-12-064527"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02567.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00168442"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.08.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706429"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2006"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb16082.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601341"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1370143"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb13251.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.33.2.411"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385526-8.00010-2"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0550170"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj0940760"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/12447"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-007-9078-7"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00293.2006"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00019.2010"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.101332"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/95.5.739"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-012-9303-x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm000020b"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257771003709569"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(03)00058-9"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1160\/TH03-06-0373","article-title":"Beneficial effects of CD39\/ecto\u2010nucleoside triphosphate diphosphohydrolase\u20101 in murine intestinal ischemia\u2010reperfusion injury","volume":"91","author":"Guckelberger O","year":"2004","journal-title":"Thromb Haemost"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm990156d"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-869520"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-8673.1996.tb00051.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-005-8076-x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4949"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.51.33116"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp265"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2003.08.007"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-005-6217-x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002680"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385526-8.00009-6"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707361"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-011-9226-y"},{"key":"e_1_2_8_46_1","first-page":"131","article-title":"A new route to nucleoside 5\u2032\u2010triphosphates","volume":"16","author":"Ludwig J","year":"1981","journal-title":"Acta Biochim Biophys Acad Sci Hung"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1143"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115485"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.043729"},{"key":"e_1_2_8_50_1","first-page":"100","article-title":"The role of adenine nucleotides in the functional activity of platelets in hemophilia A","volume":"33","author":"Mareeva TB","year":"1987","journal-title":"Vop Med Khim"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803474"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.09.003"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.07.033"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06797.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2010.12.041"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300569200"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-006-9003-5"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5640"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.8.2801"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00063-6"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000089330.88461.D6"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(01)00387-3"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.226373"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00151.2005"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03674.x"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02131.x"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.01.088"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1975.tb02750.x"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00168441"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-011-9234-0"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-205658"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.1097"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0067-4"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-012-9309-4"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.12.006"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12135","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T10:49:32Z","timestamp":1697453372000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,12]]},"references-count":74,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1111\/bph.12135"],"URL":"https:\/\/doi.org\/10.1111\/bph.12135","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,12]]},"assertion":[{"value":"2012-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}