{"id":2909,"date":"2023-06-27T14:45:38","date_gmt":"2023-06-27T05:45:38","guid":{"rendered":"https:\/\/bionauts.jp\/?p=2909"},"modified":"2023-06-27T15:53:02","modified_gmt":"2023-06-27T06:53:02","slug":"thyroid-hormone-receptor-beta-thr%ce%b2-selective-agonist","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=2909","title":{"rendered":"Thyroid Hormone Receptor-beta (THR\u03b2) Selective Agonist"},"content":{"rendered":"<h3>Advantages<\/h3>\n<ul>\n<li>Novel synthetic compound<\/li>\n<li>Higher THR\u03b2 selectivity<\/li>\n<li>Higher safety<\/li>\n<\/ul>\n<h3>Background and Technology<\/h3>\n<p>There are two subtypes of THR: \u03b1 and \u03b2. The ligand TH is known to activate cholesterol metabolism in the liver and decrease blood lipid concentrations via THR\u03b2, while binding to THR\u03b1 causes adverse effects such as arrhythmia and loss of muscle and bone mass. Therefore, TH analogs that selectively bind to THR\u03b2 may be excellent therapeutic agents with fewer side effects for NASH, dyslipidemia, and obesity. Representative THR\u03b2-selective TH analogs known so far include GC-1 (Sobetirome) and GC-24. In particular, the THR\u03b2 selectivity of GC-1 has been demonstrated in several animal models, and clinical trials as a novel cholesterol-lowering agent were conducted but discontinued due to toxicity issues.<br \/>\nWe have successfully developed a novel TH analog compound with high affinity and selectivity for THR\u03b2. The structure with enhanced hydrophobicity while maintaining a conformation favorable for binding to the receptor has resulted in high selectivity for THR\u03b2 in vitro and in vivo (bottom left). Oral administration of the compound to obese model mice with a high-fat diet showed an improvement in lipid metabolism (bottom right), and it showed no toxicity at high concentrations.<\/p>\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\/06\/BK-04471-1.png\"><img decoding=\"async\" loading=\"lazy\" class=\"alignleft size-full wp-image-2912\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1.png\" alt=\"\" width=\"2794\" height=\"865\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1.png 2794w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-300x93.png 300w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-1024x317.png 1024w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-768x238.png 768w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-1536x476.png 1536w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-2048x634.png 2048w, https:\/\/bionauts.jp\/wp-content\/uploads\/2023\/06\/BK-04471-1-1200x372.png 1200w\" sizes=\"(max-width: 709px) 85vw, (max-width: 909px) 67vw, (max-width: 1362px) 62vw, 840px\" \/><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h3>Reference and Patent<\/h3>\n<ul>\n<li>Academic paper under submission<\/li>\n<li>Patent pending<\/li>\n<\/ul>\n<h3>Principal Investigator<\/h3>\n<p>Takashi YOSHIMURA (Institute of Transformative Bio-Molecules, Nagoya University, Tokai National Higher Education and Research System)<\/p>\n<h3>Current Stage and Next Step<\/h3>\n<ul>\n<li>Currently at the stage of designing and synthesizing a new compound and confirming basic drug efficacy and safety through in vitro and in vivo experiments at the laboratory level.<\/li>\n<li>In the future, we would like to conduct feasibility studies to evaluate the potential of this compound as a therapeutic drug and are looking for partner companies to collaborate with us.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>Project No. BK-04471<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A small molecule compound that is superior to existing thyroid hormone (TH) analog compounds and applicable for the treatment of NASH, lipid metabolism disorders, and obesity.<\/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":[99,96],"other_than_medicine":[],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2909"}],"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=2909"}],"version-history":[{"count":2,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2909\/revisions"}],"predecessor-version":[{"id":2913,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/2909\/revisions\/2913"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2909"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2909"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2909"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=2909"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=2909"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=2909"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=2909"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=2909"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=2909"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=2909"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=2909"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=2909"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}