{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:12:01Z","timestamp":1782587521924,"version":"3.54.5"},"reference-count":36,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2019,2]]},"DOI":"10.1124\/mol.118.112946","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T09:50:33Z","timestamp":1542793833000},"page":"222-234","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":32,"title":["Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor \u03b2 Superfamily Type 1 Receptors"],"prefix":"10.1016","volume":"95","author":[{"given":"Lindsay C.","family":"Spender","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. John","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth D.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick W.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren S.","family":"Strathearn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen J.","family":"Sansom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Barry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6264-4253","authenticated-orcid":false,"given":"Gareth J.","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/mol.118.112946_bib1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd3810","article-title":"Targeting the TGF\u03b2 signalling pathway in disease","volume":"11","author":"Akhurst","year":"2012","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/mol.118.112946_bib2","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1177\/0192623311416259","article-title":"Induction of heart valve lesions by small-molecule ALK5 inhibitors","volume":"39","author":"Anderton","year":"2011","journal-title":"Toxicol Pathol"},{"key":"10.1124\/mol.118.112946_bib3","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.ccr.2010.10.023","article-title":"TGF-\u03b2 receptor inhibitors target the CD44(high)\/Id1(high) glioma-initiating cell population in human glioblastoma","volume":"18","author":"Anido","year":"2010","journal-title":"Cancer Cell"},{"key":"10.1124\/mol.118.112946_bib4","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1056\/NEJM200005043421807","article-title":"Role of transforming growth factor beta in human disease","volume":"342","author":"Blobe","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1124\/mol.118.112946_bib5","doi-asserted-by":"crossref","first-page":"R292","DOI":"10.1016\/S0960-9822(01)00167-1","article-title":"Epidermal growth factor receptor signaling","volume":"11","author":"Bogdan","year":"2001","journal-title":"Curr Biol"},{"key":"10.1124\/mol.118.112946_bib6","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0092-8674(00)00116-1","article-title":"Signal transduction by the JNK group of MAP kinases","volume":"103","author":"Davis","year":"2000","journal-title":"Cell"},{"key":"10.1124\/mol.118.112946_bib7","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1093\/emboj\/17.11.3091","article-title":"Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene","volume":"17","author":"Dennler","year":"1998","journal-title":"EMBO J"},{"key":"10.1124\/mol.118.112946_bib8","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s00280-015-2895-4","article-title":"Phase 1 study of galunisertib, a TGF-beta receptor I kinase inhibitor, in Japanese patients with advanced solid tumors","volume":"76","author":"Fujiwara","year":"2015","journal-title":"Cancer Chemother Pharmacol"},{"key":"10.1124\/mol.118.112946_bib9","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1021\/jm0509905","article-title":"Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor","volume":"49","author":"Gellibert","year":"2006","journal-title":"J Med Chem"},{"key":"10.1124\/mol.118.112946_bib10","doi-asserted-by":"crossref","first-page":"7901","DOI":"10.1021\/jm900807w","article-title":"Rapid generation of a high quality lead for transforming growth factor-beta (TGF-beta) type I receptor (ALK5)","volume":"52","author":"Goldberg","year":"2009","journal-title":"J Med Chem"},{"key":"10.1124\/mol.118.112946_bib11","first-page":"4479","article-title":"Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway","volume":"9","author":"Herbertz","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"10.1124\/mol.118.112946_bib12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1471-2121-10-20","article-title":"A rapid and sensitive bioassay for the simultaneous measurement of multiple bone morphogenetic proteins. Identification and quantification of BMP4, BMP6 and BMP9 in bovine and human serum","volume":"10","author":"Herrera","year":"2009","journal-title":"BMC Cell Biol"},{"key":"10.1124\/mol.118.112946_bib13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.gde.2010.12.004","article-title":"Switching TGF\u03b2 from a tumor suppressor to a tumor promoter","volume":"21","author":"Inman","year":"2011","journal-title":"Curr Opin Genet Dev"},{"key":"10.1124\/mol.118.112946_bib14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1124\/mol.62.1.65","article-title":"SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7","volume":"62","author":"Inman","year":"2002","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.118.112946_bib15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s12012-014-9297-4","article-title":"Cardiac safety of TGF-\u03b2 receptor I kinase inhibitor LY2157299 monohydrate in cancer patients in a first-in-human dose study","volume":"15","author":"Kovacs","year":"2015","journal-title":"Cardiovasc Toxicol"},{"key":"10.1124\/mol.118.112946_bib16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1517\/13543784.14.6.629","article-title":"TGF-beta inhibitors for the treatment of cancer","volume":"14","author":"Lahn","year":"2005","journal-title":"Expert Opin Investig Drugs"},{"key":"10.1124\/mol.118.112946_bib17","doi-asserted-by":"crossref","first-page":"8108","DOI":"10.1128\/MCB.25.18.8108-8125.2005","article-title":"Smad4 dependency defines two classes of transforming growth factor beta (TGF-beta) target genes and distinguishes TGF-beta-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses","volume":"25","author":"Levy","year":"2005","journal-title":"Mol Cell Biol"},{"key":"10.1124\/mol.118.112946_bib18","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1007\/s00018-006-6085-8","article-title":"Role of transforming growth factor-beta in the progression of heart failure","volume":"63","author":"Lim","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"10.1124\/mol.118.112946_bib19","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1111\/bph.13945","article-title":"Evaluating the antifibrotic potency of galunisertib in a human ex vivo model of liver fibrosis","volume":"174","author":"Luangmonkong","year":"2017","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.118.112946_bib20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s13402-014-0210-8","article-title":"Anti-tumor activity of the TGF-\u03b2 receptor kinase inhibitor galunisertib (LY2157299 monohydrate) in patient-derived tumor xenografts","volume":"38","author":"Maier","year":"2015","journal-title":"Cell Oncol (Dordr)"},{"key":"10.1124\/mol.118.112946_bib21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.arcmed.2011.08.004","article-title":"Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty liver disease: a novel approach to reduce cardiovascular risk?","volume":"42","author":"Maurantonio","year":"2011","journal-title":"Arch Med Res"},{"key":"10.1124\/mol.118.112946_bib22","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.18632\/oncotarget.2878","article-title":"SKI2162, an inhibitor of the TGF-\u03b2 type I receptor (ALK5), inhibits radiation-induced fibrosis in mice","volume":"6","author":"Park","year":"2015","journal-title":"Oncotarget"},{"key":"10.1124\/mol.118.112946_bib23","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s00018-014-1798-6","article-title":"EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-\u03b2\/Smad and ROS signaling","volume":"72","author":"Park","year":"2015","journal-title":"Cell Mol Life Sci"},{"key":"10.1124\/mol.118.112946_bib24","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ccr.2009.02.011","article-title":"TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma","volume":"15","author":"Pe\u00f1uelas","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1124\/mol.118.112946_bib25","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.31756","article-title":"TGF-\u03b2 uses a novel mode of receptor activation to phosphorylate SMAD1\/5 and induce epithelial-to-mesenchymal transition","volume":"7","author":"Ramachandran","year":"2018","journal-title":"eLife"},{"key":"10.1124\/mol.118.112946_bib26","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/nrm2297","article-title":"TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility","volume":"8","author":"Schmierer","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1124\/mol.118.112946_bib27","doi-asserted-by":"crossref","first-page":"21614","DOI":"10.18632\/oncotarget.4308","article-title":"Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients","volume":"6","author":"Serova","year":"2015","journal-title":"Oncotarget"},{"key":"10.1124\/mol.118.112946_bib36","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/laban.1257","article-title":"Design, analysis and reporting of tumor models","volume":"46","author":"Shaw","year":"2017","journal-title":"Lab Animal"},{"key":"10.1124\/mol.118.112946_bib28","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-beta signaling from cell membrane to the nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"10.1124\/mol.118.112946_bib29","doi-asserted-by":"crossref","first-page":"81995","DOI":"10.18632\/oncotarget.13226","article-title":"Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells","volume":"7","author":"Spender","year":"2016","journal-title":"Oncotarget"},{"key":"10.1124\/mol.118.112946_bib30","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ydbio.2008.07.038","article-title":"Signaling via the Tgf-beta type I receptor Alk5 in heart development","volume":"322","author":"Sridurongrit","year":"2008","journal-title":"Dev Biol"},{"key":"10.1124\/mol.118.112946_bib31","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1016\/j.cellsig.2011.06.019","article-title":"The specificities of small molecule inhibitors of the TGF\u00df and BMP pathways","volume":"23","author":"Vogt","year":"2011","journal-title":"Cell Signal"},{"key":"10.1124\/mol.118.112946_bib32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.gendis.2014.07.005","article-title":"Bone Morphogenetic Protein (BMP) signaling in development and human diseases","volume":"1","author":"Wang","year":"2014","journal-title":"Genes Dis"},{"key":"10.1124\/mol.118.112946_bib33","doi-asserted-by":"crossref","first-page":"6659","DOI":"10.18632\/oncotarget.23795","article-title":"Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-\u03b2 receptor type I inhibitor","volume":"9","author":"Yingling","year":"2017","journal-title":"Oncotarget"},{"key":"10.1124\/mol.118.112946_bib34","doi-asserted-by":"crossref","first-page":"6686","DOI":"10.1073\/pnas.111614398","article-title":"Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta","volume":"98","author":"Zavadil","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.118.112946_bib35","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/cr.2008.328","article-title":"Non-Smad pathways in TGF-beta signaling","volume":"19","author":"Zhang","year":"2009","journal-title":"Cell Res"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24008150?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24008150?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.118.112946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T10:26:04Z","timestamp":1739960764000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24008150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["S0026895X24008150"],"URL":"https:\/\/doi.org\/10.1124\/mol.118.112946","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2019,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor \u03b2 Superfamily Type 1 Receptors","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.118.112946","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}