{"id":3133,"date":"2023-09-26T15:00:13","date_gmt":"2023-09-26T06:00:13","guid":{"rendered":"https:\/\/bionauts.jp\/?p=3133"},"modified":"2023-09-26T15:16:21","modified_gmt":"2023-09-26T06:16:21","slug":"drug-repositioning-of-miglustat-for-idiopathic-pulmonary-fibrosis","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=3133","title":{"rendered":"Drug Repositioning of Miglustat for Idiopathic Pulmonary Fibrosis"},"content":{"rendered":"<h3>Advantage and Core Benefit<\/h3>\n<ul>\n<li>Different mode of action from those of existing IPF drugs, such as suppression of inflammatory cytokines and inhibition of FGFR<\/li>\n<li>Has been shown to treat not only pulmonary fibrosis but also hepatic fibrosis and is expected to expand its application to other fibroses, such as scleroderma.<\/li>\n<\/ul>\n<h3>Background and Technology<\/h3>\n<p>Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of extracellular matrix such as collagen and fibronectin by myofibroblasts differentiated from fibroblasts that have accumulated excessively. TGF-\u03b21 is a fibrosis-promoting factor that promotes fibroblast-myofibroblast differentiation (FMD), and inhibition of FMD is one of the therapeutic targets of IPF treatment.<br \/>\nIn the process of screening compounds with anti-FMD activity, the inventors showed that Miglustat, a glucosylceramide synthase (GCS) inhibitor clinically approved for the treatment of Niemann-Pick disease type C and Gaucher disease, inhibits TGF-\u03b21-induced FMD by blocking Smad2\/3 nuclear transfer. FMD by inhibiting Smad2\/3 nuclear translocation.<br \/>\nIn a mouse model of bleomycin (BLM)-induced lung fibrosis, treatment with Miglustat markedly improved the deterioration of respiratory function. Furthermore, the antifibrotic effects of Miglustat in the BLM-induced lung injury model were like those of pirfenidone and Nintedanib, which are clinically approved drugs for the treatment of IPF.<\/p>\n<h3>Data<\/h3>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 100%;\"><a href=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2023\/09\/WL-04682a.png\"><img decoding=\"async\" loading=\"lazy\" class=\"alignleft size-full wp-image-3134\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2023\/09\/WL-04682a.png\" alt=\"\" width=\"779\" height=\"486\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/09\/WL-04682a.png 779w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/09\/WL-04682a-300x187.png 300w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/09\/WL-04682a-768x479.png 768w\" sizes=\"(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 984px) 61vw, (max-width: 1362px) 45vw, 600px\" \/><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<ul>\n<li>Knockdown of GCS in human lung fibroblast HFL1 did not suppress TGF-\u03b21-induced FMD, suggesting that Miglustat exerts its anti-FMD effects by a mechanism independent of GCS inhibition.<\/li>\n<li>Pathological condition of fibrosis (A), Fibrosis score (B), hydroxyproline deposition (C) after oral administration of Miglustat (NB-DNJ: 100 mg or 300 mg\/kg), pirfenidone (200 mg\/kg), and nintedanib (60 mg\/kg) in a model of BLM-induced lung fibrosis model.<\/li>\n<\/ul>\n<h3>Patent &amp; Publication<\/h3>\n<p>JP 7109039 (Granted), US 10,478,427 (Granted), US 10,980,78 (Granted)<\/p>\n<p><a title=\"https:\/\/doi.org\/10.1016\/j.biopha.2023.114405\" href=\"https:\/\/doi.org\/10.1016\/j.biopha.2023.114405\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/j.biopha.2023.114405<\/a>, <a title=\"https:\/\/doi.org\/10.1016\/j.bbrc.2022.12.025\" href=\"https:\/\/doi.org\/10.1016\/j.bbrc.2022.12.025\" target=\"_blank\" rel=\"noopener\">https:\/\/doi.org\/10.1016\/j.bbrc.2022.12.025<\/a>.<\/p>\n<h3>Researcher<\/h3>\n<p>Dr. Hiroyuki Nakamura (Chiba University)<\/p>\n<h3>Expectations<\/h3>\n<p>Seeking companies interested in developing a drug repositioning of Miglustat for the treatment of IPF.<\/p>\n<p>&nbsp;<\/p>\n<p>Project No.WL-04682<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Mechanism of inhibition of nuclear translocation of phosphorylated Smad and induction of differentiation into Myofibroblast<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0},"categories":[1],"tags":[],"categories_of_inventions":[46],"disease_categories___indication":[],"asset_type":[],"development_phase":[],"medicine":[96],"other_than_medicine":[],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3133"}],"collection":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3133"}],"version-history":[{"count":4,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3133\/revisions"}],"predecessor-version":[{"id":3138,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3133\/revisions\/3138"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3133"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3133"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3133"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=3133"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=3133"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=3133"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=3133"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=3133"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=3133"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=3133"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=3133"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=3133"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}