{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:56:13Z","timestamp":1790142973918,"version":"4.0.1"},"reference-count":136,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR 152"],"award-info":[{"award-number":["TRR 152"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a ubiquitously expressed membrane protein, which forms a channel linked to a cytosolic protein kinase. Genetic inactivation of TRPM7 in animal models uncovered the critical role of TRPM7 in early embryonic development, immune responses, and the organismal balance of Zn2+, Mg2+, and Ca2+. TRPM7 emerged as a new therapeutic target because malfunctions of TRPM7 have been associated with anoxic neuronal death, tissue fibrosis, tumour progression, and giant platelet disorder. Recently, several laboratories have identified pharmacological compounds allowing to modulate either channel or kinase activity of TRPM7. Among other small molecules, NS8593 has been defined as a potent negative gating regulator of the TRPM7 channel. Consequently, several groups applied NS8593 to investigate cellular pathways regulated by TRPM7. Here, we summarize the progress in this research area. In particular, two notable milestones have been reached in the assessment of TRPM7 druggability. Firstly, several laboratories demonstrated that NS8593 treatment reliably mirrors prominent phenotypes of cells manipulated by genetic inactivation of TRPM7. Secondly, it has been shown that NS8593 allows us to probe the therapeutic potential of TRPM7 in animal models of human diseases. Collectively, these studies employing NS8593 may serve as a blueprint for the preclinical assessment of TRPM7-targeting drugs.<\/jats:p>","DOI":"10.3390\/ijms21197017","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"7017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Mapping TRPM7 Function by NS8593"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6042-4193","authenticated-orcid":false,"given":"Vladimir","family":"Chubanov","sequence":"first","affiliation":[{"name":"Walther-Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians Universit\u00e4t M\u00fcnchen, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gudermann","sequence":"additional","affiliation":[{"name":"Walther-Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians Universit\u00e4t M\u00fcnchen, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"4884","DOI":"10.1073\/pnas.94.10.4884","article-title":"Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase","volume":"94","author":"Ryazanov","year":"1997","journal-title":"Proc. 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