{"id":29766,"date":"2024-08-22T15:56:58","date_gmt":"2024-08-22T13:56:58","guid":{"rendered":"https:\/\/fgu.antstudio.dev\/?post_type=vyzkumny-projekt&#038;p=29766"},"modified":"2024-08-31T16:31:32","modified_gmt":"2024-08-31T14:31:32","slug":"structure-activity-guided-design-of-novel-long-acting-antagonists-of-muscarinic-receptors","status":"publish","type":"vyzkumny-projekt","link":"https:\/\/fgu.cas.cz\/en\/research-project\/structure-activity-guided-design-of-novel-long-acting-antagonists-of-muscarinic-receptors\/","title":{"rendered":"Structure-activity guided design of novel long-acting antagonists of muscarinic receptors"},"content":{"rendered":"<div>\n<div>\n<div>\n<div>\n<p>Given the broad range of functions that muscarinic receptors subserve, it is of fundamental importance to find subtype-selective ligands for therapeutic use in specific disorders.<\/p>\n<\/div>\n<\/div>\n<p><img fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-26341 aligncenter\" src=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/ga-1024x576.png\" alt=\"-\" width=\"1097\" height=\"617\" title=\"\" srcset=\"https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/ga-1024x576.png 1024w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/ga-300x169.png 300w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/ga-768x432.png 768w, https:\/\/fgu.cas.cz\/wp-content\/uploads\/2024\/08\/ga.png 1281w\" sizes=\"(max-width: 1097px) 100vw, 1097px\" \/><\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<p>Given the broad range of functions that muscarinic receptors subserve, it is of fundamental importance to find subtype-selective ligands for therapeutic use in specific disorders. Antagonists with long-residence time at receptors are acting longer which allows for a lower daily dose to reach a maximal therapeutic effect. A fundamentally novel class of antagonists are PAM-antagonists that exert positive cooperativity with endogenous neurotransmitter. PAM-antagonists preferentially block activated receptors. PAM-antagonists of muscarinic receptors have a therapeutic potential in a selective reversal of persistent excessive agonism under certain pathological conditions, like bronchospasm in asthma. We aim to delineate the molecular mechanisms underlying long-residence time and PAM-antagonism. Based on this knowledge we will design novel long-acting PAM-antagonists.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Given the broad range of functions that muscarinic receptors subserve, it is of fundamental importance to find subtype-selective ligands for therapeutic use in specific disorders. &nbsp; Given the broad range of functions that muscarinic receptors subserve, it is of fundamental importance to find subtype-selective ligands for therapeutic use in specific disorders. Antagonists with long-residence time [&hellip;]<\/p>\n","protected":false},"author":1,"template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"oddeleni":[168],"poskytovatel":[],"stav-projektu":[209],"class_list":["post-29766","vyzkumny-projekt","type-vyzkumny-projekt","status-publish","hentry","oddeleni-neurochemistry","stav-projektu-current-projects"],"acf":[],"_links":{"self":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/29766","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt"}],"about":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/types\/vyzkumny-projekt"}],"author":[{"embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/users\/1"}],"version-history":[{"count":0,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/vyzkumny-projekt\/29766\/revisions"}],"wp:attachment":[{"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/media?parent=29766"}],"wp:term":[{"taxonomy":"oddeleni","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/oddeleni?post=29766"},{"taxonomy":"poskytovatel","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/poskytovatel?post=29766"},{"taxonomy":"stav-projektu","embeddable":true,"href":"https:\/\/fgu.cas.cz\/en\/wp-json\/wp\/v2\/stav-projektu?post=29766"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}