{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:31:18Z","timestamp":1790069478217,"version":"4.0.1"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"name":"Ministry of Science and Technology, China","award":["2009ZX09102-049\/2009ZX09303-008\/2014ZX09507003-003"],"award-info":[{"award-number":["2009ZX09102-049\/2009ZX09303-008\/2014ZX09507003-003"]}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81201728"],"award-info":[{"award-number":["81201728"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81102454"],"award-info":[{"award-number":["81102454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2015,1]]},"DOI":"10.1016\/j.ejphar.2014.10.018","type":"journal-article","created":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T22:00:13Z","timestamp":1415656813000},"page":"14-21","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Carboxyamidotriazole: A novel inhibitor of both cAMP-phosphodiesterases and cGMP-phosphodiesterases"],"prefix":"10.1016","volume":"746","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1263-7431","authenticated-orcid":false,"given":"Lei","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiying","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2014.10.018_bib1","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1016\/S0022-5347(01)63299-3","article-title":"Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes","volume":"159","author":"Ballard","year":"1998","journal-title":"J. Urol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib2","doi-asserted-by":"crossref","first-page":"15020","DOI":"10.1073\/pnas.95.25.15020","article-title":"Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory","volume":"95","author":"Barad","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.10.018_bib3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0026-895X(25)15265-6","article-title":"Effects of xanthine derivatives on lipolysis and on adenosine 3\u2032,5\u2032-monophosphate phosphodiesterase activity","volume":"6","author":"Beavo","year":"1970","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib5","first-page":"437","article-title":"Phosphodiesterase inhibition by enoximone in preparations from nonfailing and failing human hearts","volume":"42","author":"Bethke","year":"1992","journal-title":"Arzneimittelforschung"},{"key":"10.1016\/j.ejphar.2014.10.018_bib6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-pharmtox-010611-134609","article-title":"Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters","volume":"53","author":"Cheepala","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bcp.2009.09.001","article-title":"Inhibition of PDE3, PDE4 and PDE7 potentiates glucocorticoid-induced apoptosis and overcomes glucocorticoid resistance in CEM T leukemic cells","volume":"79","author":"Dong","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib8","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.ceca.2004.04.004","article-title":"The blocking of capacitative calcium entry by 2-aminoethyl diphenylborate (2-APB) and carboxyamidotriazole (CAI) inhibits proliferation in Hep G2 and Huh-7 human hepatoma cells","volume":"36","author":"Enfissi","year":"2004","journal-title":"Cell Calcium"},{"key":"10.1016\/j.ejphar.2014.10.018_bib9","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1152\/physrev.00030.2010","article-title":"Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions","volume":"91","author":"Francis","year":"2011","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2014.10.018_bib10","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/978-3-642-17969-3_18","article-title":"Harnessing the clinical efficacy of phosphodiesterase 4 inhibitors in inflammatory lung diseases: dual-specific phosphodiesterase inhibitors and novel combination therapies","volume":"204","author":"Giembycz","year":"2011","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib11","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/sj.bjp.0701649","article-title":"Effects of rolipram on cyclic AMP levels in alveolar macrophages and lipopolysaccharide-induced inflammation in mouse lung","volume":"123","author":"Goncalves de Moraes","year":"1998","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib12","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1124\/jpet.107.131888","article-title":"Anti-inflammatory and analgesic potency of carboxyamidotriazole, a tumorostatic agent","volume":"325","author":"Guo","year":"2008","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejphar.2014.10.018_bib13","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1124\/jpet.112.192849","article-title":"Carboxyamidotriazole ameliorates experimental colitis by inhibition of cytokine production, nuclear factor-kappaB activation, and colonic fibrosis","volume":"342","author":"Guo","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.ejphar.2014.10.018_bib14","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.bcp.2004.05.026","article-title":"Phosphodiesterase inhibitors as anti-cancer drugs","volume":"68","author":"Hirsh","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib15","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/j.1440-1746.2009.05797.x","article-title":"The effect of sildenafil, a phosphodiesterase-5 inhibitor, on acetic acid-induced colonic inflammation in the rat","volume":"24","author":"Iseri","year":"2009","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib16","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nmeth0106-11","article-title":"Spying on cGMP with FRET","volume":"3","author":"Jalink","year":"2006","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ejphar.2014.10.018_bib17","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.ejca.2011.06.050","article-title":"Inhibition of pro-inflammatory cytokines in tumour associated macrophages is a potential anti-cancer mechanism of carboxyamidotriazole","volume":"48","author":"Ju","year":"2012","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.ejphar.2014.10.018_bib18","doi-asserted-by":"crossref","first-page":"11236","DOI":"10.1073\/pnas.93.20.11236","article-title":"Inhibition of calmodulin-dependent phosphodiesterase induces apoptosis in human leukemic cells","volume":"93","author":"Jiang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.10.018_bib19","first-page":"3208","article-title":"In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates","volume":"52","author":"Kohn","year":"1992","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejphar.2014.10.018_bib20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/BJ20051368","article-title":"Cyclic nucleotide phosphodiesterases as targets for treatment of haematological malignancies","volume":"393","author":"Lerner","year":"2006","journal-title":"Biochem. J."},{"key":"10.1016\/j.ejphar.2014.10.018_bib21","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1186\/ar3041","article-title":"Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis","volume":"12","author":"McCann","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.ejphar.2014.10.018_bib22","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1111\/j.1365-2141.1995.tb05225.x","article-title":"Theophylline, a new inducer of apoptosis in B-CLL: role of cyclic nucleotides","volume":"90","author":"Mentz","year":"1995","journal-title":"Br. J. Haematol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib23","doi-asserted-by":"crossref","first-page":"17111","DOI":"10.1073\/pnas.1108121108","article-title":"Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model","volume":"108","author":"Meyer","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejphar.2014.10.018_bib24","first-page":"H807","article-title":"Action of cAMP on expression and release of adhesion molecules in human endothelial cells","volume":"270","author":"Morandini","year":"1996","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib25","doi-asserted-by":"crossref","first-page":"37215","DOI":"10.1074\/jbc.C400302200","article-title":"Novel single chain cAMP sensors for receptor-induced signal propagation","volume":"279","author":"Nikolaev","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2014.10.018_bib27","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/978-3-642-17969-3_17","article-title":"Phosphodiesterase inhibitors in the treatment of inflammatory diseases","volume":"204","author":"Page","year":"2011","journal-title":"Handb. Exp. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib28","first-page":"2869","article-title":"Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2","volume":"24","author":"Perabo","year":"2004","journal-title":"Anticancer Res."},{"key":"10.1016\/j.ejphar.2014.10.018_bib29","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1182\/blood-2009-11-252668","article-title":"Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies","volume":"116","author":"Rickles","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.ejphar.2014.10.018_bib30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1517\/13543784.2012.658915","article-title":"Phosphodiesterase inhibitors in inflammatory bowel disease","volume":"21","author":"Salari","year":"2012","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.ejphar.2014.10.018_bib31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1517\/13543780903485642","article-title":"Targeting cancer with phosphodiesterase inhibitors","volume":"19","author":"Savai","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"10.1016\/j.ejphar.2014.10.018_bib32","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1111\/j.1476-5381.2009.00559.x","article-title":"Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis","volume":"159","author":"Schafer","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib33","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/j.1476-5381.1996.tb15450.x","article-title":"Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a \u2018low-affinity\u2019 phosphodiesterase 4 conformer","volume":"118","author":"Souness","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib34","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1111\/j.1476-5381.1994.tb14855.x","article-title":"Possible role of cyclic AMP phosphodiesterases in the actions of ibudilast on eosinophil thromboxane generation and airways smooth muscle tone","volume":"111","author":"Souness","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib35","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1083\/jcb.200605050","article-title":"PGE(1) stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases","volume":"175","author":"Terrin","year":"2006","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.ejphar.2014.10.018_bib36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1021\/bi00778a018","article-title":"Multiple cyclic nucleotide phosphodiesterase activities from rat brain","volume":"10","author":"Thompson","year":"1971","journal-title":"Biochemistry"},{"key":"10.1016\/j.ejphar.2014.10.018_bib37","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1158\/1535-7163.MCT-09-0758","article-title":"Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G","volume":"8","author":"Tinsley","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.ejphar.2014.10.018_bib38","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1183\/09031936.00055908","article-title":"Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats","volume":"33","author":"Wang","year":"2009","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.ejphar.2014.10.018_bib39","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.3109\/10428190109097725","article-title":"Carboxyamido-triazole (CAI)\u2014a novel \u201cstatic\u201d signal transduction inhibitor induces apoptosis in human B-cell chronic lymphocytic leukemia cells","volume":"42","author":"Waselenko","year":"2001","journal-title":"Leuk. Lymphoma"},{"key":"10.1016\/j.ejphar.2014.10.018_bib40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/1465-9921-6-89","article-title":"Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation","volume":"6","author":"Yao","year":"2005","journal-title":"Respir. Res."},{"key":"10.1016\/j.ejphar.2014.10.018_bib41","doi-asserted-by":"crossref","first-page":"492901","DOI":"10.1155\/2012\/492901","article-title":"Low dose theophylline showed an inhibitory effect on the production of IL-6 and IL-8 in primary lung fibroblast from patients with COPD","volume":"2012","author":"Zhang","year":"2012","journal-title":"Mediators Inflamm."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299914007250?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299914007250?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T12:33:53Z","timestamp":1747139633000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299914007250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":39,"alternative-id":["S0014299914007250"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2014.10.018","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Carboxyamidotriazole: A novel inhibitor of both cAMP-phosphodiesterases and cGMP-phosphodiesterases","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2014.10.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}