{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:43:14Z","timestamp":1789828994860,"version":"4.0.1"},"reference-count":57,"publisher":"Rockefeller University Press","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI155808"],"award-info":[{"award-number":["AI155808"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM108989"],"award-info":[{"award-number":["GM108989"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI144026"],"award-info":[{"award-number":["R01AI144026"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018378","name":"Owens Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018378","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008457","name":"University of Virginia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008457","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007267"],"award-info":[{"award-number":["T32 GM007267"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007055"],"award-info":[{"award-number":["T32 GM007055"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:p>TRPM7, a TRP channel with ion conductance and kinase activities, has emerged as an attractive drug target for immunomodulation. Reverse genetics and cell biological studies have already established a key role for TRPM7 in the inflammatory activation of macrophages. Advancing TRPM7 as a viable molecular target for immunomodulation requires selective TRPM7 inhibitors with in vivo tolerability and efficacy. Such inhibitors have the potential to interdict inflammatory cascades mediated by systemic and tissue-specialized macrophages. FTY720, an FDA-approved drug for multiple sclerosis inhibits TRPM7. However, FTY720 is a prodrug and its metabolite, FTY720-phosphate, is a potent agonist of sphingosine-1-phosphate (S1P) receptors. In this study, we test non-phosphorylatable FTY720 analogs, which are inert against S1PRs and well tolerated in vivo, for activity against TRPM7 and tissue bioavailability. Using patch clamp electrophysiology, we show that VPC01091.4 and AAL-149 block TRPM7 current at low micromolar concentrations. In culture, they act directly on macrophages to blunt LPS-induced inflammatory cytokine expression, though this likely occurrs through multiple molecular targets. We found that VPC01091.4 has significant and rapid accumulation in the brain and lungs, along with direct anti-inflammatory action on alveolar macrophages and microglia. Finally, using a mouse model of endotoxemia, we show VPC01091.4 to be an efficacious anti-inflammatory agent that arrests systemic inflammation in vivo. Together, these findings identify novel small molecule inhibitors that allow TRPM7 channel inhibition independent of S1P receptor targeting which demonstrate potent, polymodal anti-inflammatory activities ex vivo and in vivo.<\/jats:p>","DOI":"10.1085\/jgp.202313419","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T02:20:49Z","timestamp":1697854849000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Analogs of FTY720 inhibit TRPM7 but not S1PRs and exert multimodal anti-inflammatory effects"],"prefix":"10.1085","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-682X","authenticated-orcid":true,"given":"Gregory W.","family":"Busey","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5217-1942","authenticated-orcid":true,"given":"Mohan C.","family":"Manjegowda","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-0490","authenticated-orcid":true,"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3129-4542","authenticated-orcid":true,"given":"Wesley H.","family":"Iobst","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7977-0873","authenticated-orcid":true,"given":"Shardul S.","family":"Naphade","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4707-6795","authenticated-orcid":true,"given":"Joel A.","family":"Kennedy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-2371","authenticated-orcid":true,"given":"Catherine A.","family":"Doyle","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7153-4670","authenticated-orcid":true,"given":"Philip V.","family":"Seegren","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7376-922X","authenticated-orcid":true,"given":"Kevin R.","family":"Lynch","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3928-5854","authenticated-orcid":true,"given":"Bimal N.","family":"Desai","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 1 Pharmacology Department, , Charlottesville, VA, USA"},{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia School of Medicine 2 Carter Immunology Center, , Charlottesville, VA, USA"},{"id":[{"id":"https:\/\/ror.org\/0153tk833","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Virginia 3 Cardiovascular Research Center, , Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"2023110914303410700_bib1","doi-asserted-by":"publisher","first-page":"E6079","DOI":"10.1073\/pnas.1707380114","article-title":"TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles","volume":"114","author":"Abiria","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023110914303410700_bib2","doi-asserted-by":"publisher","first-page":"L709","DOI":"10.1152\/ajplung.00341.2013","article-title":"Diverse macrophage populations mediate acute lung inflammation and resolution","volume":"306","author":"Aggarwal","year":"2014","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2023110914303410700_bib3","doi-asserted-by":"publisher","first-page":"5373","DOI":"10.1021\/jm050242f","article-title":"Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomer","volume":"48","author":"Albert","year":"2005","journal-title":"J. Med. Chem."},{"key":"2023110914303410700_bib4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/B978-0-12-374841-6.00001-3","article-title":"A practical guide to the preparation of Ca(2+) buffers","volume":"99","author":"Bers","year":"2010","journal-title":"Methods Cell Biol."},{"key":"2023110914303410700_bib5","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrd3248","article-title":"Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis","volume":"9","author":"Brinkmann","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023110914303410700_bib6","doi-asserted-by":"publisher","first-page":"21453","DOI":"10.1074\/jbc.C200176200","article-title":"The immune modulator FTY720 targets sphingosine 1-phosphate receptors","volume":"277","author":"Brinkmann","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023110914303410700_bib7","doi-asserted-by":"publisher","first-page":"3154","DOI":"10.1016\/S0021-9258(19)50708-6","article-title":"Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways","volume":"267","author":"Buehrer","year":"1992","journal-title":"J. Biol. Chem."},{"key":"2023110914303410700_bib8","doi-asserted-by":"publisher","first-page":"2821","DOI":"10.4049\/jimmunol.1302269","article-title":"In vivo characterization of alveolar and interstitial lung macrophages in rhesus macaques: Implications for understanding lung disease in humans","volume":"192","author":"Cai","year":"2014","journal-title":"J. Immunol."},{"key":"2023110914303410700_bib9","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.ahj.2014.06.028","article-title":"Cardiac and vascular effects of fingolimod: Mechanistic basis and clinical implications","volume":"168","author":"Camm","year":"2014","journal-title":"Am. Heart J."},{"key":"2023110914303410700_bib10","doi-asserted-by":"publisher","first-page":"5037","DOI":"10.4049\/jimmunol.160.10.5037","article-title":"FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing","volume":"160","author":"Chiba","year":"1998","journal-title":"J. Immunol."},{"key":"2023110914303410700_bib11","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.ceca.2017.03.004","article-title":"Assessment of TRPM7 functions by drug-like small molecules","volume":"67","author":"Chubanov","year":"2017","journal-title":"Cell Calcium"},{"key":"2023110914303410700_bib12","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1111\/j.1476-5381.2012.01855.x","article-title":"Natural and synthetic modulators of SK (K(ca)2) potassium channels inhibit magnesium-dependent activity of the kinase-coupled cation channel TRPM7","volume":"166","author":"Chubanov","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"2023110914303410700_bib13","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3390\/cells3041089","article-title":"Natural and synthetic modulators of the TRPM7 channel","volume":"3","author":"Chubanov","year":"2014","journal-title":"Cells"},{"key":"2023110914303410700_bib14","doi-asserted-by":"publisher","first-page":"2894","DOI":"10.1073\/pnas.0305252101","article-title":"Disruption of TRPM6\/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia","volume":"101","author":"Chubanov","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023110914303410700_bib15","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/j.devcel.2012.04.006","article-title":"Cleavage of TRPM7 releases the kinase domain from the ion channel and regulates its participation in Fas-induced apoptosis","volume":"22","author":"Desai","year":"2012","journal-title":"Dev. Cell"},{"key":"2023110914303410700_bib16","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1161\/CIRCEP.110.957407","article-title":"Inhibition of small-conductance Ca2+-activated K+ channels terminates and protects against atrial fibrillation","volume":"3","author":"Diness","year":"2010","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"2023110914303410700_bib17","doi-asserted-by":"publisher","first-page":"E8201","DOI":"10.1073\/pnas.1810719115","article-title":"Structure of the mammalian TRPM7, a magnesium channel required during embryonic development","volume":"115","author":"Duan","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023110914303410700_bib18","doi-asserted-by":"publisher","first-page":"8806","DOI":"10.1038\/s41598-017-08144-1","article-title":"TRPM6 and TRPM7 differentially contribute to the relief of heteromeric TRPM6\/7 channels from inhibition by cytosolic Mg2+ and Mg\u00b7ATP","volume":"7","author":"Ferioli","year":"2017","journal-title":"Sci. Rep."},{"key":"2023110914303410700_bib19","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","article-title":"Ion channels in innate and adaptive immunity","volume":"33","author":"Feske","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"2023110914303410700_bib20","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1124\/jpet.107.127183","article-title":"Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: Consequences for mode of action in multiple sclerosis","volume":"323","author":"Foster","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2023110914303410700_bib21","doi-asserted-by":"publisher","first-page":"8533","DOI":"10.1007\/s00216-015-9008-4","article-title":"Quantification of sphingosine 1-phosphate by validated LC-MS\/MS method revealing strong correlation with apolipoprotein M in plasma but not in serum due to platelet activation during blood coagulation","volume":"407","author":"Frej","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"2023110914303410700_bib22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s12016-020-08824-3","article-title":"New insights on the role of TRP channels in calcium signalling and immunomodulation: Review of pathways and implications for clinical practice","volume":"60","author":"Froghi","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"2023110914303410700_bib23","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/0006-8993(93)90090-A","article-title":"Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral endotoxin treatment: Comparison with interleukin-1 family and interleukin-6","volume":"624","author":"Gatti","year":"1993","journal-title":"Brain Res."},{"key":"2023110914303410700_bib24","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1681\/ASN.2005070700","article-title":"The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens","volume":"17","author":"Groenestege","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"2023110914303410700_bib25","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/ni1008-1091","article-title":"The immunological genome Project: Networks of gene expression in immune cells","volume":"9","author":"Heng","year":"2008","journal-title":"Nat. Immunol."},{"key":"2023110914303410700_bib26","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1126\/science.1163493","article-title":"Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering Mg2+ homeostasis","volume":"322","author":"Jin","year":"2008","journal-title":"Science"},{"key":"2023110914303410700_bib27","doi-asserted-by":"publisher","first-page":"E225","DOI":"10.1073\/pnas.1120033109","article-title":"The channel kinase, TRPM7, is required for early embryonic development","volume":"109","author":"Jin","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023110914303410700_bib28","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41573-021-00268-4","article-title":"Advances in TRP channel drug discovery: From target validation to clinical studies","volume":"21","author":"Koivisto","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023110914303410700_bib29","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1085\/jgp.200509324","article-title":"Charge screening by internal pH and polyvalent cations as a mechanism for activation, inhibition, and rundown of TRPM7\/MIC channels","volume":"126","author":"Kozak","year":"2005","journal-title":"J. Gen. Physiol."},{"key":"2023110914303410700_bib30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0169-328X(94)90197-X","article-title":"Peripheral administration of lipopolysaccharide induces the expression of cytokine transcripts in the brain and pituitary of mice","volume":"27","author":"Lay\u00e9","year":"1994","journal-title":"Brain Res. Mol. Brain Res."},{"key":"2023110914303410700_bib31","article-title":"Sphingosine 1-phosphate agonists comprising cycloalkanes and 5-membered heterocycles substituted by amino and phenyl groups","author":"Lynch","year":"2006"},{"key":"2023110914303410700_bib32","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature02284","article-title":"Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1","volume":"427","author":"Matloubian","year":"2004","journal-title":"Nature"},{"key":"2023110914303410700_bib33","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abb0619","article-title":"Targeting the ion channel TRPM7 promotes the thymic development of regulatory T cells by promoting IL-2 signaling","volume":"13","author":"Mendu","year":"2020","journal-title":"Sci. Signal."},{"key":"2023110914303410700_bib34","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1124\/dmd.105.009001","article-title":"Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) in rats after oral and intravenous doses","volume":"34","author":"Meno-Tetang","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"2023110914303410700_bib35","doi-asserted-by":"publisher","first-page":"25843","DOI":"10.1074\/jbc.R200009200","article-title":"De novo sphingolipid biosynthesis: A necessary, but dangerous, pathway","volume":"277","author":"Merrill","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023110914303410700_bib36","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev-pharmtox-010617-052832","article-title":"TRP channels as potential drug targets","volume":"58","author":"Moran","year":"2018","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2023110914303410700_bib37","doi-asserted-by":"publisher","first-page":"742065","DOI":"10.3389\/fnins.2021.742065","article-title":"Microglia in neuroinflammation and neurodegeneration: From understanding to therapy","volume":"15","author":"Muzio","year":"2021","journal-title":"Front. Neurosci."},{"key":"2023110914303410700_bib38","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1038\/s41467-023-38362-3","article-title":"Structural mechanisms of TRPM7 activation and inhibition","volume":"14","author":"Nadezhdin","year":"2023","journal-title":"Nat. Commun."},{"key":"2023110914303410700_bib39","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/35079092","article-title":"LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability","volume":"411","author":"Nadler","year":"2001","journal-title":"Nature"},{"key":"2023110914303410700_bib40","doi-asserted-by":"publisher","first-page":"57287","DOI":"10.3791\/57287","article-title":"Isolation and in vitro culture of murine and human alveolar macrophages","author":"Nayak","year":"2018","journal-title":"J. Vis. Exp."},{"key":"2023110914303410700_bib41","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1161\/01.RES.0000200179.29375.cc","article-title":"Functional TRPM7 channels accumulate at the plasma membrane in response to fluid flow","volume":"98","author":"Oancea","year":"2006","journal-title":"Circ. Res."},{"key":"2023110914303410700_bib42","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/S0014-5793(03)01168-2","article-title":"The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2","volume":"554","author":"Paugh","year":"2003","journal-title":"FEBS Lett."},{"key":"2023110914303410700_bib43","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/(SICI)1097-4547(19970515)48:4&lt;287::AID-JNR1&gt;3.0.CO;2-7","article-title":"Induction of cytokine transcripts in the central nervous system and pituitary following peripheral administration of endotoxin to mice","volume":"48","author":"Pitossi","year":"1997","journal-title":"J. Neurosci. Res."},{"key":"2023110914303410700_bib44","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1111\/bph.12012","article-title":"Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels","volume":"168","author":"Qin","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"2023110914303410700_bib45","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1126\/science.1058519","article-title":"TRP-PLIK, a bifunctional protein with kinase and ion channel activities","volume":"291","author":"Runnels","year":"2001","journal-title":"Science"},{"key":"2023110914303410700_bib46","doi-asserted-by":"publisher","first-page":"13839","DOI":"10.1074\/jbc.M311743200","article-title":"Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate","volume":"279","author":"Sanna","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2023110914303410700_bib47","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1038\/s41467-022-30959-4","article-title":"Efferocytosis requires periphagosomal Ca2+-signaling and TRPM7-mediated electrical activity","volume":"13","author":"Schappe","year":"2022","journal-title":"Nat. Commun."},{"key":"2023110914303410700_bib48","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.immuni.2017.11.026","article-title":"Chanzyme TRPM7 mediates the Ca2+ influx essential for lipopolysaccharide-induced toll-like receptor 4 endocytosis and macrophage activation","volume":"48","author":"Schappe","year":"2018","journal-title":"Immunity"},{"key":"2023110914303410700_bib49","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1194\/jlr.D800051-JLR200","article-title":"Quantitative analysis of sphingolipids for lipidomics using triple quadrupole and quadrupole linear ion trap mass spectrometers","volume":"50","author":"Shaner","year":"2009","journal-title":"J. Lipid Res."},{"key":"2023110914303410700_bib50","doi-asserted-by":"publisher","first-page":"11811","DOI":"10.1021\/jacs.3c03366","article-title":"Total syntheses of (+)-Waixenicin A, (+)-9-Deacetoxy-14,15-deepoxyxeniculin, and (\u2212)-Xeniafaraunol A","volume":"145","author":"Steinborn","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"2023110914303410700_bib51","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1742-2094-1-14","article-title":"Microglia and neuroinflammation: A pathological perspective","volume":"1","author":"Streit","year":"2004","journal-title":"J. Neuroinflammation"},{"key":"2023110914303410700_bib52","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1124\/mol.106.027110","article-title":"Inhibitory gating modulation of small conductance Ca2+-activated K+ channels by the synthetic compound (R)-N-(benzimidazol-2-yl)-1,2,3,4-tetrahydro-1-naphtylamine (NS8593) reduces afterhyperpolarizing current in hippocampal CA1 neurons","volume":"70","author":"Str\u00f8baek","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"2023110914303410700_bib53","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1038\/s41401-020-00512-4","article-title":"Waixenicin A, a marine-derived TRPM7 inhibitor: A promising CNS drug lead","volume":"41","author":"Sun","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"2023110914303410700_bib54","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1007\/s12975-020-00810-3","article-title":"TRPM7 mediates neuronal cell death upstream of calcium\/calmodulin-dependent protein kinase II and calcineurin mechanism in neonatal hypoxic-ischemic brain injury","volume":"12","author":"Turlova","year":"2021","journal-title":"Transl. Stroke Res."},{"key":"2023110914303410700_bib55","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/s41573-019-0013-8","article-title":"Antibodies and venom peptides: New modalities for ion channels","volume":"18","author":"Wulff","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"2023110914303410700_bib56","doi-asserted-by":"publisher","first-page":"6428","DOI":"10.1021\/jm7010172","article-title":"Asymmetric synthesis of conformationally constrained fingolimod analogues--discovery of an orally active sphingosine 1-phosphate receptor type-1 agonist and receptor type-3 antagonist","volume":"50","author":"Zhu","year":"2007","journal-title":"J. Med. Chem."},{"key":"2023110914303410700_bib57","doi-asserted-by":"publisher","first-page":"39328","DOI":"10.1074\/jbc.M111.264341","article-title":"Waixenicin A inhibits cell proliferation through magnesium-dependent block of transient receptor potential melastatin 7 (TRPM7) channels","volume":"286","author":"Zierler","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313419\/1920717\/jgp_202313419.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313419\/1920717\/jgp_202313419.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T09:31:11Z","timestamp":1699522271000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/156\/1\/e202313419\/276399\/Analogs-of-FTY720-inhibit-TRPM7-but-not-S1PRs-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,9]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202313419","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,9]]},"article-number":"e202313419"}}