{"id":6504,"date":"2023-02-17T06:57:50","date_gmt":"2023-02-17T06:57:50","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-discovery-and-preclinical-characterization-of-usmarapride-suvn-d4010-a-potent-selective-5-ht4-receptor-partial-agonist-for-the-treatment-of-cognitive-deficits-associated-with-alzheimer\/"},"modified":"2023-02-17T06:57:50","modified_gmt":"2023-02-17T06:57:50","slug":"2021-discovery-and-preclinical-characterization-of-usmarapride-suvn-d4010-a-potent-selective-5-ht4-receptor-partial-agonist-for-the-treatment-of-cognitive-deficits-associated-with-alzheimer","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2021-discovery-and-preclinical-characterization-of-usmarapride-suvn-d4010-a-potent-selective-5-ht4-receptor-partial-agonist-for-the-treatment-of-cognitive-deficits-associated-with-alzheimer\/","title":{"rendered":"2021 &#8211; Discovery and Preclinical Characterization of Usmarapride (SUVN-D4010): A Potent, Selective 5-HT4 Receptor Partial Agonist for the Treatment of Cognitive Deficits Associated with Alzheimer\u2019s Disease"},"content":{"rendered":"<p>A series of oxadiazole derivatives were synthesized and evaluated as 5-hydroxytryptamine-4 receptor (5-HT4R) partial agonists for the treatment of cognitive deficits associated with Alzheimer\u2019s disease. Starting from a reported 5-HT4R antagonist, a systematic structure\u2013activity relationship was conducted, which led to the discovery of potent and selective 5-HT4R partial agonist 1-isopropyl-3-{5-[1-(3-methoxypropyl) piperidin-4-yl]-[1,3,4]oxadiazol-2-yl}-1H-indazole oxalate (Usmarapride, 12l). It showed balanced physicochemical\u2013pharmacokinetic properties with robust nonclinical efficacy in cognition models. It also showed disease-modifying potential, as it increased neuroprotective soluble amyloid precursor protein alpha levels, and dose-dependent target engagement and correlation of efficacy with oral exposures. Phase 1 clinical studies have been completed and projected efficacious concentration was achieved without any major safety concerns. Phase 2 enabling long-term safety studies have been completed with no concerns for further development.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[55],"target_categories":[337],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-6504","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cns","target_categories-ligand-gated-ion-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6504","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=6504"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6504"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6504"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6504"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6504"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6504"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6504"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6504"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6504"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}