{"id":13388,"date":"2023-07-28T10:44:49","date_gmt":"2023-07-28T10:44:49","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=13388"},"modified":"2024-01-11T10:45:31","modified_gmt":"2024-01-11T10:45:31","slug":"2023-structure-activity-relationship-of-dihydropyridines-for-rhabdomyosarcoma","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2023-structure-activity-relationship-of-dihydropyridines-for-rhabdomyosarcoma\/","title":{"rendered":"2023 &#8211; Structure-activity relationship of dihydropyridines for rhabdomyosarcoma"},"content":{"rendered":"<p>Childhood muscle-related cancer rhabdomyosarcoma is a rare disease with a 50-year unmet clinical need for the patients presented with advanced disease. The rarity of \u223c350 cases per year in North America generally diminishes the viability of large-scale, pharmaceutical industry driven drug development efforts for rhabdomyosarcoma. In this study, we performed a large-scale screen of 640,000 compounds to identify the\u00a0dihydropyridine\u00a0(DHP) class of anti-hypertensives as a priority compound hit. A structure-activity relationship was uncovered with increasing cell growth inhibition as side chain length increases at the ortho and para positions of the parent DHP molecule. Growth inhibition was consistent across n\u00a0=\u00a021 rhabdomyosarcoma cell line models. Anti-tumor activity\u00a0<em>in\u00a0vitro<\/em>\u00a0was paralleled by studies\u00a0<em>in\u00a0vivo<\/em>. The unexpected finding was that the action of DHPs appears to be other than on the DHP receptor (<em>i.e.<\/em>, L-type voltage-gated calcium channel). These findings provide the basis of a medicinal chemistry program to develop\u00a0dihydropyridine\u00a0derivatives that retain anti-rhabdomyosarcoma activity without anti-hypertensive effects.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[57,254],"target_categories":[61],"target_families":[340],"targets":[91,106,107],"resource_keyword":[],"class_list":["post-13388","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-rare-diseases","target_categories-voltage-gated-ion-channels","target_families-cav-channels","targets-cav1-2","targets-cav2-2","targets-cav3-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/13388","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=13388"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=13388"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=13388"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=13388"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=13388"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=13388"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=13388"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=13388"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=13388"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}