{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:34:01Z","timestamp":1776425641242,"version":"3.51.2"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Signalling"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.cellsig.2020.109881","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T03:15:37Z","timestamp":1607397337000},"page":"109881","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"special_numbering":"C","title":["Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti-fibrotic treatment options in a mouse model of tubulointerstitial fibrosis"],"prefix":"10.1016","volume":"79","author":[{"given":"Stephanie","family":"Schwalm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Redona","family":"Hafizi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Trautmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Geisslinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Pyne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Pyne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Huwiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"Pfeilschifter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"10159","key":"10.1016\/j.cellsig.2020.109881_bb0005","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/S0140-6736(18)31694-5","article-title":"Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016\u201340 for 195 countries and territories","volume":"392","author":"Foreman","year":"2018","journal-title":"Lancet."},{"issue":"4","key":"10.1016\/j.cellsig.2020.109881_bb0010","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.cmet.2012.06.017","article-title":"Sphingolipid signaling in metabolic disorders","volume":"16","author":"Hla","year":"2012","journal-title":"Cell Metab."},{"issue":"1","key":"10.1016\/j.cellsig.2020.109881_bb0015","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.tcb.2011.09.003","article-title":"Sphingosine-1-phosphate signaling and its role in disease","volume":"22","author":"Maceyka","year":"2012","journal-title":"Trends Cell Biol."},{"issue":"1","key":"10.1016\/j.cellsig.2020.109881_bb0020","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.bbalip.2012.07.022","article-title":"Sphingosine-1-phosphate: a Janus-faced mediator of fibrotic diseases","volume":"1831","author":"Schwalm","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"issue":"1","key":"10.1016\/j.cellsig.2020.109881_bb0025","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.bbalip.2012.07.003","article-title":"Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis","volume":"1831","author":"Pyne","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"10.1016\/j.cellsig.2020.109881_bb0030","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.matbio.2018.01.006","article-title":"Sphingolipid signaling in renal fibrosis","volume":"68\u201369","author":"Huwiler","year":"2018","journal-title":"Matrix Biol."},{"issue":"34","key":"10.1016\/j.cellsig.2020.109881_bb0035","doi-asserted-by":"crossref","first-page":"35255","DOI":"10.1074\/jbc.M312091200","article-title":"Sphingosine 1-phosphate cross-activates the Smad signaling cascade and mimics transforming growth factor-beta-induced cell responses","volume":"279","author":"Xin","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"5\u20136","key":"10.1016\/j.cellsig.2020.109881_bb0040","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00210-007-0132-3","article-title":"Regulation and functional roles of sphingosine kinases","volume":"374","author":"Alemany","year":"2007","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"10.1016\/j.cellsig.2020.109881_bb0045","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.biocel.2017.07.011","article-title":"Sphingosine kinase 1 protects renal tubular epithelial cells from renal fibrosis via induction of autophagy","volume":"90","author":"Du","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"issue":"8","key":"10.1016\/j.cellsig.2020.109881_bb0050","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/ki.2009.297","article-title":"Transforming growth factor-beta2 upregulates sphingosine kinase-1 activity, which in turn attenuates the fibrotic response to TGF-beta2 by impeding CTGF expression","volume":"76","author":"Ren","year":"2009","journal-title":"Kidney Int."},{"issue":"15","key":"10.1016\/j.cellsig.2020.109881_bb0055","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1093\/hmg\/dds172","article-title":"Loss of GM3 synthase gene, but not sphingosine kinase 1, is protective against murine nephronophthisis-related polycystic kidney disease","volume":"21","author":"Natoli","year":"2012","journal-title":"Hum. Mol. Genet."},{"issue":"11","key":"10.1016\/j.cellsig.2020.109881_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.ajpath.2017.06.017","article-title":"Sphingosine kinase-2 deficiency ameliorates kidney fibrosis by up-regulating Smad7 in a mouse model of unilateral ureteral obstruction","volume":"187","author":"Schwalm","year":"2017","journal-title":"Am. J. Pathol."},{"issue":"11","key":"10.1016\/j.cellsig.2020.109881_bb0065","doi-asserted-by":"crossref","first-page":"3824","DOI":"10.1016\/j.bbadis.2018.09.007","article-title":"Sphingosine kinase 2 cooperating with Fyn promotes kidney fibroblast activation and fibrosis via STAT3 and AKT","volume":"1864","author":"Zhu","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"10.1016\/j.cellsig.2020.109881_bb0070","article-title":"Sphingosine kinase 2 deficiency attenuates kidney fibrosis via IFN-\u03b3","author":"Bajwa","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"issue":"3","key":"10.1016\/j.cellsig.2020.109881_bb0075","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0194053","article-title":"Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction. Long D, ed","volume":"13","author":"Ghosh","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.cellsig.2020.109881_bb0080","series-title":"Topographical Mapping of Isoform-Selectivity Determinants for J-Channel-Binding Inhibitors of Sphingosine Kinases 1 and 2","author":"Adams","year":"2019"},{"issue":"2","key":"10.1016\/j.cellsig.2020.109881_bb0085","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/ki.2012.115","article-title":"The intrinsic prostaglandin E2\u2013EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice","volume":"82","author":"Nakagawa","year":"2012","journal-title":"Kidney Int."},{"issue":"6","key":"10.1016\/j.cellsig.2020.109881_bb0090","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1172\/JCI72267","article-title":"Cellular and molecular mechanisms in kidney fibrosis","volume":"124","author":"Duffield","year":"2014","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.cellsig.2020.109881_bb0095","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1124\/jpet.115.225862","article-title":"Sphingosine kinase 2 inhibition and blood sphingosine 1-phosphate levels","volume":"355","author":"Kharel","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"11","key":"10.1016\/j.cellsig.2020.109881_bb0100","doi-asserted-by":"crossref","first-page":"2992","DOI":"10.1681\/ASN.2006050420","article-title":"Renal fibroblasts and myofibroblasts in chronic kidney disease","volume":"17","author":"Strutz","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"issue":"6","key":"10.1016\/j.cellsig.2020.109881_bb0105","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1046\/j.1523-1755.1999.00775.x","article-title":"Interferon-\u03b3 inhibits experimental renal fibrosis","volume":"56","author":"Oldroyd","year":"1999","journal-title":"Kidney Int."},{"issue":"34","key":"10.1016\/j.cellsig.2020.109881_bb0110","doi-asserted-by":"crossref","first-page":"54240","DOI":"10.18632\/oncotarget.11095","article-title":"Interferon gamma peptidomimetic targeted to interstitial myofibroblasts attenuates renal fibrosis after unilateral ureteral obstruction in mice","volume":"7","author":"Poosti","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"10.1016\/j.cellsig.2020.109881_bb0115","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1021\/cb5008426","article-title":"Drugging sphingosine kinases","volume":"10","author":"Santos","year":"2015","journal-title":"ACS Chem. Biol."},{"issue":"1","key":"10.1016\/j.cellsig.2020.109881_bb0120","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1124\/jpet.109.163444","article-title":"Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2","volume":"333","author":"French","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"11","key":"10.1016\/j.cellsig.2020.109881_bb0125","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.1210\/en.2010-0420","article-title":"Antiestrogenic effects of the novel sphingosine Kinase-2 inhibitor ABC294640","volume":"151","author":"Antoon","year":"2010","journal-title":"Endocrinology."},{"issue":"7","key":"10.1016\/j.cellsig.2020.109881_bb0130","doi-asserted-by":"crossref","first-page":"678","DOI":"10.4161\/cbt.11.7.14903","article-title":"Targeting NF\u03baB mediated breast cancer chemoresistance through selective inhibition of sphingosine kinase-2","volume":"11","author":"Antoon","year":"2011","journal-title":"Cancer Biol. Ther."},{"issue":"4","key":"10.1016\/j.cellsig.2020.109881_bb0135","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1021\/jm501760d","article-title":"Structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors: discovery of SphK1- and SphK2-selective inhibitors","volume":"58","author":"Patwardhan","year":"2015","journal-title":"J. Med. Chem."},{"issue":"5","key":"10.1016\/j.cellsig.2020.109881_bb0140","doi-asserted-by":"crossref","first-page":"815","DOI":"10.2215\/CJN.12991117","article-title":"Glucocorticoids in the treatment of glomerular diseases: pitfalls and pearls","volume":"13","author":"Ponticelli","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"issue":"4","key":"10.1016\/j.cellsig.2020.109881_bb0145","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCRESAHA.115.306901","article-title":"Sphingosine 1-phosphate produced by sphingosine Kinase 2 intrinsically controls platelet aggregation in vitro and in vivonovelty and significance","volume":"117","author":"Urtz","year":"2015","journal-title":"Circ. Res."},{"issue":"2","key":"10.1016\/j.cellsig.2020.109881_bb0150","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.bbrc.2011.08.070","article-title":"Activation of sphingosine kinase 2 is an endogenous protective mechanism in cerebral ischemia","volume":"413","author":"Pfeilschifter","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Cellular Signalling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656820303582?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0898656820303582?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:57:43Z","timestamp":1760266663000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0898656820303582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":30,"alternative-id":["S0898656820303582"],"URL":"https:\/\/doi.org\/10.1016\/j.cellsig.2020.109881","relation":{},"ISSN":["0898-6568"],"issn-type":[{"value":"0898-6568","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti-fibrotic treatment options in a mouse model of tubulointerstitial fibrosis","name":"articletitle","label":"Article Title"},{"value":"Cellular Signalling","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellsig.2020.109881","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"109881"}}