{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363388844848337024.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1111/j.1476-5381.2010.00828.x"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1476-5381.2010.00828.x"}},{"identifier":{"@type":"URI","@value":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2010.00828.x"}},{"identifier":{"@type":"URI","@value":"https://bpspubs.onlinelibrary.wiley.com/doi/full-xml/10.1111/j.1476-5381.2010.00828.x"}}],"dc:title":[{"@value":"A novel, orally active LPA\n                    <sub>1</sub>\n                    receptor antagonist inhibits lung fibrosis in the mouse bleomycin model"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n                    <jats:bold>Background and purpose: </jats:bold>\n                    The aim of this study was to assess the potential of an antagonist selective for the lysophosphatidic acid receptor, LPA\n                    <jats:sub>1</jats:sub>\n                    , in treating lung fibrosis We evaluated the\n                    <jats:italic>in vitro</jats:italic>\n                    and\n                    <jats:italic>in vivo</jats:italic>\n                    pharmacological properties of the high affinity, selective, oral LPA\n                    <jats:sub>1</jats:sub>\n                    ‐antagonist (4′‐{4‐[(R)‐1‐(2‐chloro‐phenyl)‐ethoxycarbonylamino]‐3‐methyl‐isoxazol‐5‐yl}‐biphenyl‐4‐yl)‐acetic acid (AM966).\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Experimental approach: </jats:bold>\n                    The potency and selectivity of AM966 for LPA\n                    <jats:sub>1</jats:sub>\n                    receptors was determined\n                    <jats:italic>in vitro</jats:italic>\n                    by calcium flux and cell chemotaxis assays using recombinant and native cell cultures. The\n                    <jats:italic>in vivo</jats:italic>\n                    efficacy of AM966 to reduce tissue injury, vascular leakage, inflammation and fibrosis was assessed at several time points in the mouse bleomycin model.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Key results: </jats:bold>\n                    AM966 was a potent antagonist of LPA\n                    <jats:sub>1</jats:sub>\n                    receptors, with selectivity for this receptor over the other LPA receptors.\n                    <jats:italic>In vitro</jats:italic>\n                    , AM966 inhibited LPA‐stimulated intracellular calcium release (IC\n                    <jats:sub>50</jats:sub>\n                    = 17 nM) from Chinese hamster ovary cells stably expressing human LPA\n                    <jats:sub>1</jats:sub>\n                    receptors and inhibited LPA‐induced chemotaxis (IC\n                    <jats:sub>50</jats:sub>\n                    = 181 nM) of human IMR‐90 lung fibroblasts expressing LPA\n                    <jats:sub>1</jats:sub>\n                    receptors. AM966 demonstrated a good pharmacokinetic profile following oral dosing in mice. In the mouse, AM966 reduced lung injury, vascular leakage, inflammation and fibrosis at multiple time points following intratracheal bleomycin instillation. AM966 also decreased lactate dehydrogenase activity and tissue inhibitor of metalloproteinase‐1, transforming growth factor β1, hyaluronan and matrix metalloproteinase‐7, in bronchoalveolar lavage fluid.\n                  </jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions and implications: </jats:bold>\n                    These findings demonstrate that AM966 is a potent, selective, orally bioavailable LPA\n                    <jats:sub>1</jats:sub>\n                    receptor antagonist that may be beneficial in treating lung injury and fibrosis, as well as other diseases that are characterized by pathological inflammation, oedema and fibrosis.\n                  </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380009142498179721","@type":"Researcher","foaf:name":[{"@value":"JS Swaney"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337034","@type":"Researcher","foaf:name":[{"@value":"C Chapman"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337032","@type":"Researcher","foaf:name":[{"@value":"LD Correa"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337024","@type":"Researcher","foaf:name":[{"@value":"KJ Stebbins"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337027","@type":"Researcher","foaf:name":[{"@value":"RA Bundey"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337038","@type":"Researcher","foaf:name":[{"@value":"PC Prodanovich"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337030","@type":"Researcher","foaf:name":[{"@value":"P Fagan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337033","@type":"Researcher","foaf:name":[{"@value":"CS Baccei"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337036","@type":"Researcher","foaf:name":[{"@value":"AM Santini"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337035","@type":"Researcher","foaf:name":[{"@value":"JH Hutchinson"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337031","@type":"Researcher","foaf:name":[{"@value":"TJ Seiders"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337026","@type":"Researcher","foaf:name":[{"@value":"TA Parr"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337037","@type":"Researcher","foaf:name":[{"@value":"P Prasit"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337028","@type":"Researcher","foaf:name":[{"@value":"JF Evans"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388844848337029","@type":"Researcher","foaf:name":[{"@value":"DS Lorrain"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00071188"},{"@type":"EISSN","@value":"14765381"}],"prism:publicationName":[{"@value":"British Journal of Pharmacology"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2010-04-29","prism:volume":"160","prism:number":"7","prism:startingPage":"1699","prism:endingPage":"1713"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor","http://doi.wiley.com/10.1002/tdm_license_1.1"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1476-5381.2010.00828.x"},{"@id":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2010.00828.x"},{"@id":"https://bpspubs.onlinelibrary.wiley.com/doi/full-xml/10.1111/j.1476-5381.2010.00828.x"}],"createdAt":"2010-04-30","modifiedAt":"2026-03-08","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050005822287192064","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lysophosphatidic acid LPA1 and LPA3 receptors play roles in the maintenance of late tissue plasminogen activator-induced central poststroke pain in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1050282810927666432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Sphingosine-1-phosphate as a mediator involved in development of fibrotic diseases"}]},{"@id":"https://cir.nii.ac.jp/crid/1050304183896200704","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Lysophosphatidic Acid Receptor 1- and 3-Mediated Hyperalgesia and Hypoalgesia in Diabetic Neuropathic Pain Models in Mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1360004231995378304","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts"}]},{"@id":"https://cir.nii.ac.jp/crid/1360009142498180224","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Druggable Lysophospholipid Signaling Pathways"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021390752988032","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"LPA receptor-mediated signaling regulates cell motility and survival to anticancer drug of pancreatic cancer cells under glucose-deprived and hypoxic conditions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021390754741120","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cellular functions modulated by endothelial cells in pancreatic cancer cells under hypoxic conditions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285706972063360","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Current progress in non-Edg family LPA receptor research"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285708506893568","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lys39-Lysophosphatidate Carbonyl Oxygen Interaction Locks LPA1 N-terminal Cap to the Orthosteric Site and partners Arg124 During Receptor Activation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360286991702001408","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effects of lysophosphatidic acid (LPA) receptor-2 (LPA2) and LPA3 on the regulation of chemoresistance to anticancer drug in lung cancer cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360290617810319488","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lysophosphatidic acid induces thrombospondin‐1 production in primary cultured rat cortical astrocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360294643799001728","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"An ATX-LPA6-Gα13-ROCK axis shapes and maintains caudal vein plexus in zebrafish"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181997587200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lysophosphatidylethanolamine utilizes LPA1 and CD97 in MDA-MB-231 breast cancer cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380583238656","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lysophosphatidic acid (LPA) receptor-mediated signaling regulates hypoxia-induced biological functions of lymphatic endothelial cells"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848656201605376","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lysophosphatidic acid induces anxiety-like behavior via its receptors in mice"}]},{"@id":"https://cir.nii.ac.jp/crid/1361975846570590208","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The component changes of lysophospholipid mediators in colorectal cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282680235112320","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Lysophosphatidic acid (LPA) signaling through LPA<SUB>1</SUB> in organ fibrosis: A pathway with pleiotropic pro-fibrotic effects"},{"@value":"Lysophosphatidic acid (LPA) signaling through LPA1 in organ fibrosis: A pathway with pleiotropic pro-fibrotic effects"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1111/j.1476-5381.2010.00828.x"},{"@type":"CROSSREF","@value":"10.1016/j.cellsig.2013.07.001_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.2492/inflammregen.33.078_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.bbalip.2012.06.008_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1007/978-3-030-50621-6_7_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2023.04.036_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.prp.2024.155192_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1038/srep13343_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.bbalip.2014.05.004_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1111/jnc.15227_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.isci.2021.103254_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.cellsig.2020.109551_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.3390/cells9081906_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2024.149982_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1007/s00702-014-1289-9_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.ynpai.2018.07.001_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1016/j.bbalip.2012.08.003_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"},{"@type":"CROSSREF","@value":"10.1177/1010428319848616_references_DOI_IEhaRT7UdtilGEbpwrlvXoOj8iA"}]}