{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:25:21Z","timestamp":1790774721423,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Pepducins are membrane-tethered, cell-penetrating lipopeptides that target the cytoplasmic surface of their cognate receptor. Here, we report the first human use of a protease-activated receptor-1\u2013based pepducin, which is intended as an antiplatelet agent to prevent ischemic complications of percutaneous coronary interventions.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>PZ-128 was administered by 1 to 2 hours continuous intravenous infusion (0.01\u20132 mg\/kg) to 31 subjects with coronary artery disease or multiple coronary artery disease risk factors. Safety, antiplatelet efficacy, and pharmacokinetics were assessed at baseline and 0.5, 1, 2, 6, 24 hours, and 7 to 10 days postdosing. The inhibitory effects of PZ-128 on platelet aggregation stimulated by the protease-activated receptor-1 agonist SFLLRN (8 \u03bcmol\/L) at 30 minutes to 6 hours were dose dependent with 20% to 40% inhibition at 0.3 mg\/kg, 40% to 60% at 0.5 mg\/kg, and \u226580% to 100% at 1 to 2 mg\/kg. The subgroup receiving aspirin in the 0.5 and 1-mg\/kg dose cohorts had 65% to 100% inhibition of final aggregation to SFLLRN at 30 minutes to 2 hours and 95% to 100% inhibition by 6 hours. The inhibitory effects of 0.5 mg\/kg PZ-128 were reversible with 50% recovery of aggregation to SFLLRN by 24 hours. There were no significant effects of PZ-128 on aggregation induced by AYPGKF, ADP, or collagen, indicating that the observed effects were specific to protease-activated receptor-1. The plasma half-life was 1.3 to 1.8 hours, and PZ-128 was nondetectable in urine. There were no effects on bleeding, coagulation, clinical chemistry, or ECG parameters.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>PZ-128 is a promising antiplatelet agent that provides rapid, specific, dose dependent, and reversible inhibition of platelet protease-activated receptor-1 through a novel intracellular mechanism.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT01806077.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306777","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T21:25:35Z","timestamp":1450905935000},"page":"189-197","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease"],"prefix":"10.1161","volume":"36","author":[{"given":"Paul A.","family":"Gurbel","sequence":"first","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Bliden","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Turner","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udaya S.","family":"Tantry","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"Gesheff","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis P.","family":"Barr","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidija","family":"Covic","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athan","family":"Kuliopulos","sequence":"additional","affiliation":[{"name":"From the Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T., M.G.G.); and the Center for Hemostasis and Thrombosis Research, MORI, Tufts Medical Center, Boston, MA (S.E.T., T.P.B., L.C., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000157138.02645.11"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.031195"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303412"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.574830"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.110.959098"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3385"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.4.437"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2004.11.011"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.091918"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.853135"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.07.101"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv104"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61170-8"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.09.017"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.587758"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60230-0"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq320"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109719"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm760"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1525"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.636316"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022460899"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.355461"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5480.739"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07330"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11701"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.02.018"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-919-2_19"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.12.1520"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.12.029"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2013.10.037"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-07-0624"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.000786"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.001404"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.07.041"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.115.306777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:08:48Z","timestamp":1715555328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.115.306777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1]]}},"alternative-id":["10.1161\/ATVBAHA.115.306777"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.115.306777","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1]]},"assertion":[{"value":"2015-10-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}