{"id":6400,"date":"2023-02-17T06:57:22","date_gmt":"2023-02-17T06:57:22","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-discovery-and-development-of-suvn-911-a-novel-potent-selective-and-orally-active-neuronal-nicotinic-acetylcholine-%ce%b14%ce%b22-receptor-antagonist-for-the-treatment-of-depression\/"},"modified":"2023-02-17T06:57:22","modified_gmt":"2023-02-17T06:57:22","slug":"2020-discovery-and-development-of-suvn-911-a-novel-potent-selective-and-orally-active-neuronal-nicotinic-acetylcholine-%ce%b14%ce%b22-receptor-antagonist-for-the-treatment-of-depression","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2020-discovery-and-development-of-suvn-911-a-novel-potent-selective-and-orally-active-neuronal-nicotinic-acetylcholine-%ce%b14%ce%b22-receptor-antagonist-for-the-treatment-of-depression\/","title":{"rendered":"2020 &#8211; Discovery and Development of SUVN-911: A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine \u03b14\u03b22 Receptor Antagonist for the Treatment of Depression"},"content":{"rendered":"<p>A series of chemical optimizations guided by in vitro affinity at the \u03b14\u03b22 receptor in combination with selectivity against the \u03b13\u03b24 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent \u03b14\u03b22 receptor ligand with a Ki value of 1.5 nM. It showed >10 \u03bcM binding affinity toward the ganglionic \u03b13\u03b24 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its 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":[360],"targets":[188,194],"resource_keyword":[],"class_list":["post-6400","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","target_families-nicotinic-acetylcholine-receptors","targets-achr-3-4","targets-achr-4-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6400","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=6400"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6400"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6400"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6400"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6400"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6400"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6400"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6400"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6400"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}