{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:11:12Z","timestamp":1769436672428,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T00:00:00Z","timestamp":1516147200000},"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":[[2018,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Autotaxin (ATX) is a secreted phospholipase which hydrolyses lysophosphatidylcholine to generate lysophosphatidic acid (LPA). The extracellular signalling molecule LPA exerts its biological actions through activation of six GPCRs expressed in various cell types including fibroblasts. Multiple preclinical studies using knockout animals, LPA receptor antagonists or ATX inhibitors have provided evidence for a potential role of the ATX\/LPA axis in tissue fibrosis. Despite growing evidence for a correlation between ATX levels and the degree of fibrosis in chronic liver diseases, including viral hepatitis and hepatocellular carcinoma, the role of ATX in non\u2010alcoholic steatohepatitis (NASH) remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The relevance of ATX in the pathogenesis of liver fibrosis was investigated by oral administration of Ex_31, a selective ATX inhibitor, in a 10\u00a0week model of carbon tetrachloride\u2010induced liver injury and in a 14\u00a0week model of choline\u2010deficient amino acid\u2010defined diet\u2010induced liver injury in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Oral administration of Ex_31, a selective ATX inhibitor, at 15\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> twice daily in therapeutic intervention mode resulted in efficient ATX inhibition and more than 95% reduction in plasma LPA levels in both studies. Treatment with Ex_31 had no effect on biomarkers of liver function, inflammation, or fibrosis and did not result in histological improvements in diseased animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings question the role of ATX in the pathogenesis of hepatic fibrosis and the potential of small molecule ATX inhibitors for the treatment of patients with NASH and advanced stages of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14118","type":"journal-article","created":{"date-parts":[[2017,12,2]],"date-time":"2017-12-02T05:02:37Z","timestamp":1512190957000},"page":"693-707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Characterization of the properties of a selective, orally bioavailable autotaxin inhibitor in preclinical models of advanced stages of liver fibrosis"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8772-712X","authenticated-orcid":false,"given":"Manuel","family":"Baader","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Bretschneider","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Broermann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg F","family":"Rippmann","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Stierstorfer","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian A","family":"Kuttruff","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Mark","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH &amp; Co. KG  Biberach an der Riss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.237156"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/abio.2001.5063"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2015.02.001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200407123"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472555217690484"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01599"},{"key":"e_1_2_10_10_1","first-page":"17117","article-title":"Autotaxin\u2010LPA receptor axis in the pathogenesis of lung diseases","volume":"8","author":"Chu X","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00079.2013"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3977-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28973"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.90431.2008"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3200"},{"key":"e_1_2_10_17_1","unstructured":"KhannaD DentonCP JagerschmidtA JassonM DistlerO AllanoreY(2014).SAR100842 an antagonist of lysophaphatidic acid receptor 1 as a potential treatment for patients with systemic sclerosis: results from a phase 2a study. In ACR\/ARHP Annual Meeting. Boston MA."},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12678"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.03.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v8.i16.673"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.11.010"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00411-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2015.01.004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110397358"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-319-20538-0_4","volume-title":"Alcoholic and Non\u2010Alcoholic Fatty Liver Disease: Bench to Bedside","author":"Maher JJ","year":"2016"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02419-05"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2011.03.014"},{"key":"e_1_2_10_31_1","unstructured":"NoelB RigouG DegallaixN DaixV CambulaL RoudotAet al. (2015).Elafibranor (GFT505) prevents nash hepatic fibrosis and hepatocarcinoma in a new disease model. In The Liver Meeting 2015 \u2013 AASLD. San Francisco CA."},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(01)00110-1"},{"key":"e_1_2_10_33_1","unstructured":"PasquinelliC(2013).Safety and efficacy of a lysophosphatidic acid receptor antagonist (bMS 986020) in idiopathic pulmonary fibrosis. In PFF Summit. San Diego CA."},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R046391"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103532"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25789"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.113779"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.07.019"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-387"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605142200"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2002.5657"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.08.013"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.01.013"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3634"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.14118","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.14118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T09:30:03Z","timestamp":1695893403000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.14118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,17]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/bph.14118"],"URL":"https:\/\/doi.org\/10.1111\/bph.14118","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,17]]},"assertion":[{"value":"2017-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}