{"id":16548,"date":"2024-12-02T08:23:06","date_gmt":"2024-12-02T08:23:06","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=16548"},"modified":"2024-12-02T08:23:06","modified_gmt":"2024-12-02T08:23:06","slug":"2024-ion-channel-modulator-dpi-201-106-significantly-enhances-anti-tumour-activity-of-dna-damage-response-inhibitors-in-glioblastoma","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2024-ion-channel-modulator-dpi-201-106-significantly-enhances-anti-tumour-activity-of-dna-damage-response-inhibitors-in-glioblastoma\/","title":{"rendered":"2024 &#8211; Ion channel modulator DPI-201-106 significantly enhances anti-tumour activity of DNA damage response inhibitors in glioblastoma"},"content":{"rendered":"<div class=\" sec\">\n<div class=\"title\"><strong>Background:\u00a0<\/strong>Glioblastoma, a lethal high-grade glioma, has not seen improvements in clinical outcomes in nearly 30 years. Ion channels are increasingly associated with tumourigenesis, and there are hundreds of brain-penetrant drugs that inhibit ion channels, representing an untapped therapeutic resource. The aim of this exploratory drug study was to screen an ion channel drug library against patient-derived glioblastoma cells to identify new treatments for brain cancer.<\/div>\n<\/div>\n<div class=\" sec\">\n<div><\/div>\n<div class=\"title\"><strong>Methods:\u00a0<\/strong>72 ion channel inhibitors were screened in patient-derived glioblastoma cells, and cell viability was determined using the ViaLight Assay. Cell cycle and apoptosis analysis was determined with flow cytometry using PI and Annexin V staining, respectively. Protein and phosphoprotein expression was determined using mass spectrometry and analysed by gene set enrichment analysis. Kaplan-Meier survival analyses were performed using intracranial xenograft models of GBM6 and WK1 cells.<\/div>\n<\/div>\n<div class=\" sec\">\n<div><\/div>\n<div class=\"title\"><strong>Results:\u00a0<\/strong>The voltage-gated sodium channel modulator, DPI-201-106, was revealed to reduce glioblastoma cell viability\u00a0<em>in vitro<\/em>\u00a0by inducing cell cycle arrest and apoptosis. Phosphoproteomics indicated that DPI-201-106 may impact DNA damage response pathways. Combination treatment of DPI-201-106 with the CHK1 inhibitor prexasertib or the PARP inhibitor niraparib demonstrated synergistic effects in multiple patient-derived glioblastoma cells both\u00a0<em>in vitro<\/em>\u00a0and in intracranial xenograft mouse models, extending survival of glioblastoma-bearing mice.<\/div>\n<\/div>\n<div class=\" sec\">\n<div><\/div>\n<div class=\"title\"><strong>Conclusion: <\/strong>DPI-201-106 enhances the efficacy of DNA damage response inhibitors to reduce glioblastoma growth. As these drugs have already been clinically tested in humans, repurposing DPI-201-106 in novel combinatorial approaches will allow for rapid translation into the clinic.<\/div>\n<\/div>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[57,143],"target_categories":[61],"target_families":[333],"targets":[],"resource_keyword":[],"class_list":["post-16548","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cancer","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-kv-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/16548","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=16548"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=16548"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=16548"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=16548"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=16548"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=16548"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=16548"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=16548"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=16548"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}