{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:46:03Z","timestamp":1792003563558,"version":"4.4.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2023,7,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Inhibition of PCSK9 (proprotein convertase subtilisin\/kexin type 9)-low density lipoprotein receptor interaction with injectable monoclonal antibodies or small interfering RNA lowers plasma low density lipoprotein-cholesterol, but despite nearly 2 decades of effort, an oral inhibitor of PCSK9 is not available. Macrocyclic peptides represent a novel approach to target proteins traditionally considered intractable to small-molecule drug design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Novel mRNA display screening technology was used to identify lead chemical matter, which was then optimized by applying structure-based drug design enabled by novel synthetic chemistry to identify macrocyclic peptide (MK-0616) with exquisite potency and selectivity for PCSK9. Following completion of nonclinical safety studies, MK-0616 was administered to healthy adult participants in a single rising-dose Phase 1 clinical trial designed to evaluate its safety, pharmacokinetics, and pharmacodynamics. In a multiple-dose trial in participants taking statins, MK-0616 was administered once daily for 14 days to characterize the safety, pharmacokinetics, and pharmacodynamics (change in low density lipoprotein cholesterol).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      MK-0616 displayed high affinity (\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>i<\/jats:sub>\n                      = 5pM) for PCSK9 in vitro and sufficient safety and oral bioavailability preclinically to enable advancement into the clinic. In Phase 1 clinical studies in healthy adults, single oral doses of MK-0616 were associated with &gt;93% geometric mean reduction (95% CI, 84\u2013103) of free, unbound plasma PCSK9; in participants on statin therapy, multiple\u2013oral-dose regimens provided a maximum 61% geometric mean reduction (95% CI, 43\u201385) in low density lipoprotein cholesterol from baseline after 14 days of once-daily dosing of 20 mg MK-0616.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This work validates the use of mRNA display technology for identification of novel oral therapeutic agents, exemplified by the identification of an oral PCSK9 inhibitor, which has the potential to be a highly effective cholesterol lowering therapy for patients in need.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.063372","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T05:00:15Z","timestamp":1682917215000},"page":"144-158","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":170,"title":["Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor"],"prefix":"10.1161","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8726-8514","authenticated-orcid":true,"given":"Douglas G.","family":"Johns","sequence":"first","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2373-802X","authenticated-orcid":true,"given":"Louis-Charles","family":"Campeau","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-2705","authenticated-orcid":true,"given":"Puja","family":"Banka","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Bautmans","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0911-8756","authenticated-orcid":true,"given":"Tjerk","family":"Bueters","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-6912","authenticated-orcid":true,"given":"Elisabetta","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Peptide &amp; Small Molecules R&amp;D, IRBM S.p.A., Pomezia (RM), Italy (E.B., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-597X","authenticated-orcid":true,"given":"Danila","family":"Branca","sequence":"additional","affiliation":[{"name":"Peptide &amp; Small Molecules R&amp;D, IRBM S.p.A., Pomezia (RM), Italy (E.B., D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Bulger","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inne","family":"Crevecoeur","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fa-Xiang","family":"Ding","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2240-3380","authenticated-orcid":true,"given":"Robert M.","family":"Garbaccio","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik D.","family":"Guetschow","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."},{"name":"Now with Cayman Chemical Company, Ann Arbor, MI (E.D.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sookhee N.","family":"Ha","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Johnston","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6072-7258","authenticated-orcid":true,"given":"Hubert","family":"Josien","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunkyung A.","family":"Kauh","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-4448","authenticated-orcid":true,"given":"Kenneth A.","family":"Koeplinger","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-6010","authenticated-orcid":true,"given":"Jeffrey T.","family":"Kuethe","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-3452","authenticated-orcid":true,"given":"Eseng","family":"Lai","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Lanning","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita Y.H.","family":"Lee","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anilkumar G.","family":"Nair","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-7092","authenticated-orcid":true,"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0387-8885","authenticated-orcid":true,"given":"David A.","family":"Thaisrivongs","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5616-0802","authenticated-orcid":true,"given":"Thomas J.","family":"Tucker","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-8421","authenticated-orcid":true,"given":"Petr","family":"Vachal","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristien","family":"van Dyck","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic P.","family":"Vanhoutte","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, SGS Life Sciences, Antwerp, Belgium (F.P.V., B.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7967-2915","authenticated-orcid":true,"given":"Bram","family":"Volckaert","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, SGS Life Sciences, Antwerp, Belgium (F.P.V., B.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis G.","family":"Wolford","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Xu","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhao","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Zhou","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Zhu","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hratch J.","family":"Zokian","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-136X","authenticated-orcid":true,"given":"Abbas M.","family":"Walji","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8281-0159","authenticated-orcid":true,"given":"Harold B.","family":"Wood","sequence":"additional","affiliation":[{"name":"MRL, Merck &amp; Co., Inc., Rahway, NJ (D.G.J., L.-C.C., P.B., A.B., T.B., P.G.B., I.C., F.-X.D., R.M.G., E.D.G., Y.G., S.N.H., J.M.J., H.J., E.A.K., K.A.K., J.T.K., E.L., C.L.L., A.Y.H.L., L.L., A.G.N., E.A.O., S.A.S., D.A.T., T.J.T., P.V., K.v.D., D.G.W., A.X., T.Z., D.Z., S.Z., X.Z., H.J.Z., A.M.W., H.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/C2019-0-03217-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2014.10.003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0053-0"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.10.011"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-017-2516-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113925"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2017.04.012"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.09.017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67394-1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz962"},{"key":"e_1_3_3_12_2","unstructured":"WHO. Cardiovascular Diseases (CVDs). Accessed July 13 2022. https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.06.005"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx144"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.06.010"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615758"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60771-5"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01290"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01599"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph7020207"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01084"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2011.205"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.002"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.002"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.09.019"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105685"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.09.006"},{"key":"e_1_3_3_28_2","first-page":"362","article-title":"Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells.","volume":"284","author":"Lindmark T","year":"1998","unstructured":"Lindmark, T, Kimura, Y, Artursson, P. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther. 1998;284:362\u2013369.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.08.986"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700437-JLR200"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.RV17012"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2023.02.018"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.122.063372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T04:12:00Z","timestamp":1715573520000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.122.063372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,11]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,7,11]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.122.063372"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.122.063372","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,11]]},"assertion":[{"value":"2022-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}