{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:00:08Z","timestamp":1787166008923,"version":"build-2736575974"},"reference-count":137,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Semicarbazide\u2010sensitive amine oxidase (SSAO) is a vascular enzyme and expressed in high concentrations in vascular smooth muscle cells (VSMCs), localized in the caveolae of the plasma membrane, and the endothelial cells. SSAO is classified as a copper amine oxidase and encoded by the amine oxidase copper\u2010containing 3 gene. SSAO exists both as a soluble protein and as a tissue\u2010bound transmembrane protein. The latter is often called vascular adhesion protein 1. Vascular adhesion protein\u20101 or VAP\u20101, encoded by the AOC3 gene, is a pro\u2010inflammatory and multifunctional molecule belonging to the SSAO family. It assists the transformation of primary amines to aldehydes resulting in the production of hydrogen peroxide and ammonia. Work from the last two decades, has shown that VAP\u20101\/SSAO plays a role in several physiological and pathological processes, making it a potentially valuable target for therapeutic development. In this review, we provide a detailed overview of the inhibitors of VAP\u20101\/SSAO that are being developed specifically for the treatment of inflammatory diseases. Here in we have highlighted important aspects of the compounds investigated in therapeutic applications. Furthermore, we have outlined potential avenues for innovation with the aim of maximizing the therapeutic efficacy of VAP\u20101\/SSAO inhibitors in clinical settings.<\/jats:p>","DOI":"10.1002\/med.22118","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:25:49Z","timestamp":1747805149000},"page":"1564-1596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic Potential of Vascular Adhesion Protein\u20101 (VAP\u20101)\/Semicarbazide\u2010Sensitive Amine Oxidase (SSAO) Inhibitors: Current Medicinal Chemistry and Emerging Opportunities"],"prefix":"10.1002","volume":"45","author":[{"given":"Pinaki","family":"Bhattacharjee","sequence":"first","affiliation":[{"name":"Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-4619","authenticated-orcid":false,"given":"Malliga R.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9014192"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2013.12.022"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ympev.2019.106571"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-009-0135-2"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1744309110041515"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-378630-2.00182-1"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)01870-1"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7418"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12111563"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S460605"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22073365"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.15.3893"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/11.12.1195"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1529341"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.051438105"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0240com"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02288-8"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.3.1549"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(03)00064-5"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00209-X"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1705"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200526351"},{"key":"e_1_2_14_24_1","first-page":"341","article-title":"Amine Oxidase Activities in Bovine Lung","volume":"32","author":"Lizcano J. M.","year":"1990","journal-title":"Journal of Neural Transmission. Supplementum"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830251014"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-007-0684-x"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9857"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2255"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1346-2"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.01.027"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905028805"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1107\/S090744490300979X"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm401372d"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25061293"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi200117z"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-1006-z"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9MT00148D"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2020.02.002"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00312.2016"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029270"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006519"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540104900208"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.413"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.3.1085-1094.2003"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2010-3395"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111057298"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.004889"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox5030025"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5MT00149H"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.679707"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-02-0684"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-003-0802-6"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050970"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0562fje"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.01.014"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1024\/0301-1526\/a001031"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20092358"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080612"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-020-00756-y"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64501-4"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73722"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-020-00379-x"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2015.04.007"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5197376"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.238030"},{"key":"e_1_2_14_66_1","unstructured":"C.HanAge\u2010 Sex\u2010and Glucose\u2010Dependent Correlation of Plasma Soluble Vascular."},{"key":"e_1_2_14_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.584623"},{"key":"e_1_2_14_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.02.014"},{"key":"e_1_2_14_69_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357660"},{"key":"e_1_2_14_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.04.074"},{"key":"e_1_2_14_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-007-0697-5"},{"key":"e_1_2_14_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04181.x"},{"key":"e_1_2_14_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.01.017"},{"key":"e_1_2_14_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-019-0392-1"},{"key":"e_1_2_14_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-018-0172-4"},{"key":"e_1_2_14_76_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901794"},{"key":"e_1_2_14_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1310-8"},{"key":"e_1_2_14_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535300"},{"key":"e_1_2_14_79_1","unstructured":"D. J.Smith M.Jalkanen F.Fulop et al. Biotie Therapies Corp. Inhibitors of Copper\u2010Containing Amine Oxidases. WO0202090A2 January 10 2002."},{"key":"e_1_2_14_80_1","unstructured":"Fulop L.Lazar M.Pihlavisto et al. Biotie Therapies Corp. Hydrazino Alcohol Derivatives Useful as Inhibitors of Copper\u2010Containing Amine Oxidases. WO2005080319 September 1 2005."},{"key":"e_1_2_14_81_1","unstructured":"T.Salminen T.Airenne M.Johnson et al. Biotie Therapies Corp. Crystalline VAP\u20101 and Uses Thereof. WO2004104191A1 December 2 2004."},{"key":"e_1_2_14_82_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm100337z"},{"key":"e_1_2_14_83_1","unstructured":"D.Smith M.Jalkanen F.F\u00fcl\u00f6p et al. Biotie Therapies Corp. Inhibitors of Copper\u2010Containing Amine Oxidases. WO2002002541A2 January 10 2002."},{"key":"e_1_2_14_84_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm200059p"},{"key":"e_1_2_14_85_1","unstructured":"E. Y.Wang D. S.Jones A. M.O'rourke et al. La Jolla Pharmaceutical Company. Inhibitors of Semicarbazide\u2010Sensitive Amine Oxidase(SSAO) and VAP\u20101 Mediated Adhesion Useful for Treatment and Prevention of Diseases. WO2007120528A2 October 25 2007."},{"key":"e_1_2_14_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050538l"},{"key":"e_1_2_14_87_1","unstructured":"T.Matsukawa K.Masuzaki Y.Kawai et al. R\u2010tech Ueno Ltd. Thiazole Derivative and Use Thereof as VAP\u20101 Inhibitor. WO2009096609A1 August 6 2009."},{"key":"e_1_2_14_88_1","unstructured":"T.Inoue T.Tojo andM.Morit Thiazole Derivatives Having VAP\u20101 Inhibitory Activity. WO2006028269A2 March 16 2006."},{"key":"e_1_2_14_89_1","unstructured":"T.Inoue T.Tojo andM.Morit Thiazole Derivatives Having VAP\u20101 Inhibitory Activity. WO2006011631A2 February 2 2006."},{"key":"e_1_2_14_90_1","unstructured":"T.Inoue T.Tojo andM.Morit Thiazole Derivatives and Their Use as VAP\u20101 Inhibitors. WO2004067521A1 August 12 2004."},{"key":"e_1_2_14_91_1","unstructured":"R.Ueno A.Nagashima T.Inoue M.Ohkubo K.Yoshihara Method for Treating Vascular Hyperpermeable Disease WO2004087138A1 October 14 2004."},{"key":"e_1_2_14_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2012.12.025"},{"key":"e_1_2_14_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.02.048"},{"key":"e_1_2_14_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.04.011"},{"key":"e_1_2_14_95_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198911163212004"},{"key":"e_1_2_14_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.04.111"},{"key":"e_1_2_14_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2022.128942"},{"key":"e_1_2_14_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90293-R"},{"key":"e_1_2_14_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2011.05.026"},{"key":"e_1_2_14_100_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.207613"},{"key":"e_1_2_14_101_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0200-z"},{"key":"e_1_2_14_102_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2011.594040"},{"key":"e_1_2_14_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.10.025"},{"key":"e_1_2_14_104_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712801323180"},{"key":"e_1_2_14_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2023.117558"},{"key":"e_1_2_14_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.09.036"},{"key":"e_1_2_14_107_1","unstructured":"S.Jalkanen Compositions Useful Especially for Treatment and Prevention of Metabolic Syndrome. WO2008\/025870 A1 March 6 2008."},{"key":"e_1_2_14_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e21839"},{"key":"e_1_2_14_109_1","unstructured":"S.Jalkanen M.Jalkanen andM.Salmi Compounds for Treating or Preventing Amine Oxidase Related Diseases or Disorders. WO2006134203A1 December 21 2006."},{"key":"e_1_2_14_110_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-007-0637-5"},{"key":"e_1_2_14_111_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043365305"},{"key":"e_1_2_14_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64558-0"},{"key":"e_1_2_14_113_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424932"},{"key":"e_1_2_14_114_1","unstructured":"S.Jalkanen M.Salmi M.\u2010L.Laukkanen andM. R.Clark Biotie Therapies Corp. Novel Humanized Anti\u2010VAP\u20101 Monoclonal Antibody. WO2003093319A1 November 13 2003."},{"key":"e_1_2_14_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62300-0"},{"key":"e_1_2_14_116_1","unstructured":"D.Smith P.Vainio J.Mikkola P.Vuorio andJ.Vainio \u201cBiotie Therapies Corp. Novel Fully Human Anti\u2010VAP\u20101 Monoclonal Antibodies. WO2008129124A1 December 30 2008."},{"key":"e_1_2_14_117_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708785133022"},{"key":"e_1_2_14_118_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(85)90142-9"},{"key":"e_1_2_14_119_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90145-1"},{"key":"e_1_2_14_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2010.03.006"},{"key":"e_1_2_14_121_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051076e"},{"key":"e_1_2_14_122_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0269"},{"key":"e_1_2_14_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.07.008"},{"key":"e_1_2_14_124_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1976.tb10305.x"},{"key":"e_1_2_14_125_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800393"},{"key":"e_1_2_14_126_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00232a035"},{"key":"e_1_2_14_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/1357-2725(95)00130-1"},{"key":"e_1_2_14_128_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0499211"},{"key":"e_1_2_14_129_1","unstructured":"https:\/\/clinicaltrials.gov\/(accessed Jan 2 2024)."},{"key":"e_1_2_14_130_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2005.pto_96605.x"},{"key":"e_1_2_14_131_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-311076"},{"key":"e_1_2_14_132_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-015081"},{"key":"e_1_2_14_133_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-019-0178-7"},{"key":"e_1_2_14_134_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-021-00288-7"},{"key":"e_1_2_14_135_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42398-w"},{"key":"e_1_2_14_136_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-024-03017-0"},{"key":"e_1_2_14_137_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.02.034"},{"key":"e_1_2_14_138_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30289-4"}],"container-title":["Medicinal Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/med.22118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T12:48:46Z","timestamp":1759841326000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/med.22118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":137,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/med.22118"],"URL":"https:\/\/doi.org\/10.1002\/med.22118","archive":["Portico"],"relation":{},"ISSN":["0198-6325","1098-1128"],"issn-type":[{"value":"0198-6325","type":"print"},{"value":"1098-1128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"2024-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}