{"id":3855,"date":"2024-08-09T15:06:23","date_gmt":"2024-08-09T06:06:23","guid":{"rendered":"https:\/\/bionauts.jp\/?p=3855"},"modified":"2024-08-24T01:44:07","modified_gmt":"2024-08-23T16:44:07","slug":"fusion-protein-anticancer-drug-targeting-ras","status":"publish","type":"post","link":"https:\/\/bionauts.jp\/?p=3855","title":{"rendered":"Fusion Protein Anticancer Drug Targeting RAS"},"content":{"rendered":"<h3>Advantages<\/h3>\n<ul>\n<li>Inhibits and degrades undruggable RAS<\/li>\n<li>Can be applied to all RAS (Pan-RAS) except G12C mutant RAS<\/li>\n<\/ul>\n<h3>Current Stage and Key Data<\/h3>\n<table style=\"border-collapse: collapse; width: 100%;\">\n<tbody>\n<tr>\n<td style=\"width: 50%;\">\n<ul>\n<li>\u00a0Early preclinical research stage.<\/li>\n<li>The lead compound (fusion protein X) suppresses RAS function and reduces RAS levels in vitro.<\/li>\n<li>Intravenous administration of X to syngeneic tumor-bearing model mice showed a high antitumor effect (see figure on the right).<\/li>\n<\/ul>\n<\/td>\n<td style=\"width: 50%;\"><a href=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2024\/08\/BK-04936en.png\"><img decoding=\"async\" loading=\"lazy\" class=\"alignleft size-full wp-image-3863\" src=\"http:\/\/bionauts.jp\/wp-content\/uploads\/2024\/08\/BK-04936en.png\" alt=\"\" width=\"545\" height=\"396\" srcset=\"https:\/\/bionauts.jp\/wp-content\/uploads\/2024\/08\/BK-04936en.png 545w, https:\/\/bionauts.jp\/wp-content\/uploads\/2024\/08\/BK-04936en-300x218.png 300w\" sizes=\"(max-width: 545px) 85vw, 545px\" \/><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<h3>Partnering Model<\/h3>\n<ul>\n<li>Looking for an exclusive license partner for the fusion protein X.<\/li>\n<li>A feasibility study can be conducted by signing a CDA or MTA for evaluation.<\/li>\n<li>If further optimization research of the protein is required, a collaborative study can be conducted.<\/li>\n<\/ul>\n<h3>Background and Technology<\/h3>\n<p>RAS (H-Ras, K-Ras, N-Ras) is a cancer gene that is mutated to an active form in approximately 30% of cancers, and the development of Ras inhibitors has been progressing worldwide. However, many attempts, including small molecule compounds, have failed. In 2021, a small molecule compound (sotorasib) that inhibits G12C mutant Ras was approved by the FDA. The unique feature of sotorasib is that it inhibits the function of Ras by forming a covalent bond with the mutated cysteine \u200b\u200bresidue. However, the remaining approximately 90% of \u201cNon-G12C\u201d mutant Ras is still a difficult target for drug development.<\/p>\n<p>In 2020, we reported that a protein fused with a RAS binding domain (RBD) and a cell membrane-penetrating peptide (CPP) inhibits the binding between RAS and downstream signaling molecules, but the antitumor activity was insufficient (*1). This time, the newly developed protein X fused with a third domain suppressed the function of active RAS and showed high antitumor effects.<\/p>\n<h3>Principal Investigator<\/h3>\n<p>Ryo Honda (The Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Tokai National Higher Education and Research System). *Specializes in the design and synthesis of artificial proteins.<\/p>\n<h3>Reference<\/h3>\n<ul>\n<li>Paper*1: Nomura et.al., Cell Chemical Biology 28, no. 11 (2021): 1581-1589.<\/li>\n<li>Patent application*1: WO2022\/039026<\/li>\n<li>New fusion protein X: Paper submitted, patent application filed (unpublished)<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p>Project.BK-04936<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Fusion protein X, which combines a RAS-binding domain, a cell membrane-permeable peptide, and a third domain, inhibits the function of activated RAS and degrades it.<\/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":[121,112],"other_than_medicine":[],"material":[],"engineering":[],"software_it":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3855"}],"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=3855"}],"version-history":[{"count":8,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3855\/revisions"}],"predecessor-version":[{"id":3866,"href":"https:\/\/bionauts.jp\/index.php?rest_route=\/wp\/v2\/posts\/3855\/revisions\/3866"}],"wp:attachment":[{"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3855"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3855"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3855"},{"taxonomy":"categories_of_inventions","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories_of_inventions&post=3855"},{"taxonomy":"disease_categories___indication","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdisease_categories___indication&post=3855"},{"taxonomy":"asset_type","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fasset_type&post=3855"},{"taxonomy":"development_phase","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fdevelopment_phase&post=3855"},{"taxonomy":"medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedicine&post=3855"},{"taxonomy":"other_than_medicine","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fother_than_medicine&post=3855"},{"taxonomy":"material","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmaterial&post=3855"},{"taxonomy":"engineering","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fengineering&post=3855"},{"taxonomy":"software_it","embeddable":true,"href":"https:\/\/bionauts.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fsoftware_it&post=3855"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}