{"id":6438,"date":"2023-02-23T22:49:08","date_gmt":"2023-02-24T03:49:08","guid":{"rendered":"https:\/\/dalriadatx.com\/?post_type=articles&#038;p=6438"},"modified":"2024-02-19T16:45:22","modified_gmt":"2024-02-19T21:45:22","slug":"small-molecule-highlights-08-february-2023","status":"publish","type":"articles","link":"https:\/\/dalriadatx.com\/articles\/small-molecule-highlights-08-february-2023\/","title":{"rendered":"Small Molecule Highlights #08 \u2013 February 2023"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"6438\" class=\"elementor elementor-6438\" data-elementor-post-type=\"articles\">\n\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-2468c2c elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"2468c2c\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-4e137d8 jltma-glass-effect-no\" data-id=\"4e137d8\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-882929c jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"882929c\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.20.0 - 26-03-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-2468c2c elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"2468c2c\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-4e137d8 jltma-glass-effect-no\" data-id=\"4e137d8\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-882929c jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"882929c\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p>The following list of 9 molecules, out of various drug discovery journals, have been primarily identified through the use of structure-based drug design strategies (SBDD), including X-ray co-crystal analysis, molecular modelling, receptor-ligand docking, and large-scales virtual screens. Altogether, these compounds have been designed to bind a diverse set of targets, including proteosome <b>\u03b25, CES Notum, CDK2, IDO1, THR- \u03b2, MC4R, MCH, USP21, and FGFR<\/b>. Interestingly, several of these molecules have been designed to modulate neurological circuits of appetite, weight loss, and food intake (hyperphagia, anorexia, and cachexia).<\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-d3e7f11 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"d3e7f11\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-4140dc5 jltma-glass-effect-no\" data-id=\"4140dc5\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-cc4a065 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"cc4a065\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.20.0 - 26-03-2024 *\/\n.elementor-widget-image{text-align:center}.elementor-widget-image a{display:inline-block}.elementor-widget-image a img[src$=\".svg\"]{width:48px}.elementor-widget-image img{vertical-align:middle;display:inline-block}<\/style>\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"800\" height=\"612\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-1024x783.jpg\" class=\"attachment-large size-large wp-image-6422\" alt=\"\" srcset=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-1024x783.jpg 1024w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-300x229.jpg 300w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-768x587.jpg 768w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-1536x1175.jpg 1536w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-431x330.jpg 431w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-235x180.jpg 235w, https:\/\/dalriadatx.com\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager.jpg 1718w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Small Molecule Highlights #08 \u2013 February 2023<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-e2c4e9e elementor-align-center jltma-glass-effect-no elementor-widget elementor-widget-button\" data-id=\"e2c4e9e\" data-element_type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-button-wrapper\">\n\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"\/wp-content\/uploads\/Small-Molecule-Highlights-08-one-pager-with-summary.pdf\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t<span class=\"elementor-button-text\">Download Summary<\/span>\n\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-530f9b5 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"530f9b5\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-e1435c1 jltma-glass-effect-no\" data-id=\"e1435c1\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4b59dbf jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"4b59dbf\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-530f9b5 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"530f9b5\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-e1435c1 jltma-glass-effect-no\" data-id=\"e1435c1\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-4b59dbf jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"4b59dbf\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>C2<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-fc3ef58 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"fc3ef58\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-e024f63 jltma-glass-effect-no\" data-id=\"e024f63\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-cbfaf9d jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"cbfaf9d\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/C2-q2m4ovo68a48in5vhv35lfpbul83pdq54f1kcfjdoc.jpg\" title=\"C2\" alt=\"C2\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">C2<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>C2: <\/strong>This naphthyl-azo-tricyclic-urea-based small molecule was recently reported as a proteosome \u03b25 inhibitor. Through targeting the Ubiquitin-proteosome pathway (UPP), <strong>C2 <\/strong>is being developed for therapeutic utility in oncology, neurology, and autoimmune disease. Identified through a virtual screen of a natural product ZINC library (<em>N = <\/em>5000) and a structure-based design strategy, a \u03b25 IC<sub>50<\/sub> of 3.43 \u03bcM was reported, with a K<sub>i<\/sub> of 1.15 \u03bcM (in a purified enzymatic assay). Molecular docking predicted key intermolecular stacking interactions at the \u03b25c site with Tyr169, and the \u03b25i site with Phe124, and Tyr130.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1039\/D2MD00404F\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1039\/D2MD00404F<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-4dee8b7 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"4dee8b7\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-336a628 jltma-glass-effect-no\" data-id=\"336a628\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-b31fab9 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"b31fab9\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-4dee8b7 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"4dee8b7\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-336a628 jltma-glass-effect-no\" data-id=\"336a628\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-b31fab9 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"b31fab9\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>Compound 4W<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-e4fa9f4 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"e4fa9f4\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-5bf3641 jltma-glass-effect-no\" data-id=\"5bf3641\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-6f335da jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"6f335da\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/Compound-4W-q2m4on7mirsnm5i5v9figzu6i4dss3sk39670xvx8c.jpg\" title=\"Compound 4W\" alt=\"Compound 4W\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Compound 4W<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-3bc7a82 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"3bc7a82\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-2194942 jltma-glass-effect-no\" data-id=\"2194942\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-fd9c1bc jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fd9c1bc\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>Compound 4W: <\/strong>A collaboration between the University College London (UCL), and Oxford University in the UK has recently identified this <em>N-<\/em>acyl-indoline as\u00a0 carboxylesterase Notum inhibitor. CES Notum has been implicated in Wnt signalling, with therapeutic utility in oncology. This small molecule was discovered through a structure-based strategy from a covalent <em>hit<\/em> compound (Methyl ester electrophile), and a co-crystal of a structural analog (PDB 8BT8). This analysis identified a stacking interaction with Phe268, as well as a bridging H<sub>2<\/sub>O-mediated H-bond. Against Notum-OPTS, an IC<sub>50<\/sub> of 4.9 nM was reported, and in a cellular TCF-LEF assay, an EC<sub>50<\/sub> of 22 nM was found. This compound has a LogD<sub>7.4<\/sub> of 3.1, PBS solubility of 0.4 \u03bcg\/mL and a plasma stability T<sub>1\/2\u00ad <\/sub>of &gt; 4 hrs.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115132\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1016\/j.ejmech.2023.115132<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-c839ef1 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"c839ef1\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-cb2f3ee jltma-glass-effect-no\" data-id=\"cb2f3ee\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5d1148b jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"5d1148b\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-c839ef1 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"c839ef1\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-cb2f3ee jltma-glass-effect-no\" data-id=\"cb2f3ee\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-5d1148b jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"5d1148b\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>QR-6401<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-113cca6 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"113cca6\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-f26cbd4 jltma-glass-effect-no\" data-id=\"f26cbd4\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-53246b6 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"53246b6\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/QR-6401-q2m4oo5gpltxxrgspru51hln3i95zswafdtoi7uj24.jpg\" title=\"QR-6401\" alt=\"QR-6401\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">QR-6401<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-6d5c75b elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"6d5c75b\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-404490c jltma-glass-effect-no\" data-id=\"404490c\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5bd1fae jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"5bd1fae\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>QR-6401: <\/strong>This macrocycle was recently reported a potent and selective inhibitor of cyclin-dependent kinase 2 (CKD2). The authors cited prospective therapeutic utility in CDK2-dependent cancers, and combating CCNE1 drug resistance. The design of this molecule was accelerated from hit-to-lead through the use of computational macrocycle generation models, and structure-based drug design. Against CDK2\/E1, an IC<sub>50<\/sub> of 0.37 nM was found, while against CDK1\/A2, an IC<sub>50<\/sub> of 22 nM was found (59x selective). In a cellular OVCAR3 viability study, an IC<sub>50<\/sub> of 34 nM was found, and against human liver microsomes (HLM), a T<sub>1\/2\u00ad <\/sub>of 150 mins was established. In OVCAR3 xenografts, at 50 mg\/kg (BID) using oral gavage, a TGI of 78% was found.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1021\/acsmedchemlett.2c00515\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1021\/acsmedchemlett.2c00515<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-dd7e8a2 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"dd7e8a2\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7687991 jltma-glass-effect-no\" data-id=\"7687991\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-1c8a196 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"1c8a196\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-dd7e8a2 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"dd7e8a2\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7687991 jltma-glass-effect-no\" data-id=\"7687991\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-1c8a196 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"1c8a196\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>Compound 3<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-193ac36 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"193ac36\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-a362edb jltma-glass-effect-no\" data-id=\"a362edb\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-70e8d19 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"70e8d19\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/Compound-3-1-q2m4op3awfv89dffka8rlzd3ow4j7i00rih5zht4vw.jpg\" title=\"Compound 3\" alt=\"Compound 3\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Compound 3<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-4b1c729 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"4b1c729\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-42a9042 jltma-glass-effect-no\" data-id=\"42a9042\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-40cac09 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"40cac09\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>Compound 3: <\/strong>This Oxadiazole carboximidamide was reported as an indoleamine dioxygenase 1 (IDO1) inhibitor. IDO1 is a heme-containing enzyme, involved in Trp\/Kyn metabolism and implicated in oncology. This small molecule was discovered via a structure-based strategy, through structural analogs of FDA-approved clinical standard Epacadostat (PDB 5WN8). In a biochemical assay against <em>h<\/em>IDO1, an IC<sub>50<\/sub> of 67.4 nM was found, and in a cellular HeLa IDO1 study, an IC<sub>50<\/sub> of 17.6 nM was reported. Weak cellular activity was observed in various cell lines: HeLa, HCT116, and CT26, with IC<sub>50<\/sub> values of 46.1, 19.6 and 34.9 \u03bcM. <em>In vivo<\/em> efficacy was found in LLC xenografts at 200 mg\/kg (BID) (p.o.) with a TGI of 53.07%.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1016\/j.ejmech.2023.115217\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1016\/j.ejmech.2023.115217<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>Compound 15<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-d8c5720 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"d8c5720\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-400f980 jltma-glass-effect-no\" data-id=\"400f980\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-e22794f jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"e22794f\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/Compound-15-q2m4oq1539wikze2esne6h4ka9zwf73r3n4ngrrqpo.jpg\" title=\"Compound 15\" alt=\"Compound 15\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Compound 15<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-d522f80 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"d522f80\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-3f5a9c9 jltma-glass-effect-no\" data-id=\"3f5a9c9\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-2203579 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"2203579\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>Compound 15: <\/strong>This pyrrolopyridin-5-one has been reported as an agonist of thyroid hormone receptor \u03b2, which is implicated in nonalcoholic steatohepatitis (NASH). Using a structure-based structure of a related structural analog (PDB 1N46), an EC<sub>50<\/sub> against THR-\u03b1 was found to be 220 nM, while the desired target THR- \u03b2 was 30 nM (11.2x selectivity window). At 30 mg\/kg (p.o.), a T<sub>1\/2\u00ad <\/sub>of 8.7 hrs was found, with a T<sub>Max<\/sub> of 8 hrs and a C<sub>Max<\/sub> of 2820 ng\/mL. <em>In vivo<\/em>, cholesterol reducing activity was observed, at 33.5% with a dose of 30 mg\/kg (oral gavage).<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01669\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01669<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-25da639 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"25da639\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-648a628 jltma-glass-effect-no\" data-id=\"648a628\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-a6b2bdc jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"a6b2bdc\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>BAY-805<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-df7090c elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"df7090c\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-c68fd7b jltma-glass-effect-no\" data-id=\"c68fd7b\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-27a41c7 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"27a41c7\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/BAY-805-q2m4orwtgxz387bc3tgnbgnhh1qmulb7rwfmfboyd8.jpg\" title=\"BAY-805\" alt=\"BAY-805\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">BAY-805<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8b1f017 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8b1f017\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-66bc73e jltma-glass-effect-no\" data-id=\"66bc73e\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-41e6d55 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"41e6d55\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>BAY-805: <\/strong>Bayer recently reported this 1,3,4-thiadiazol-based small molecule as a ubiquitin-specific protease inhibitor targeting USP21. This deubiquitinating enzyme (DUB) has been well-established as a validated oncology target. Using a screening cascade, starting with a 5 million compound high throughput screen towards a 10K library of primary hits, followed by a 2.5K library of secondary hits, an analog was identified with an <em>h<\/em>USP21 HTRF IC<sub>50<\/sub> of 11.8 \u03bcM. Ultimately, this was optimized towards BAY-805, with an IC\u00ad<sub>50\u00ad <\/sub>of 6 nM (~2000x improvement). In a SPR assay, a K<sub>d<\/sub> of 2.2 nM was found, and in a Ub-Rhod <em>h<\/em>USP21 study, an IC<sub>50<\/sub> of 2 nM was reported. Also, in a NF-\u03baB reporter assay, an EC<sub>50<\/sub><sup>\u00a0<\/sup>\u00a0of 16.6 nM was established.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01933\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01933<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-7242c3f elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"7242c3f\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-52272b7 jltma-glass-effect-no\" data-id=\"52272b7\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-65e6aa8 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"65e6aa8\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>Compound 2E<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-a997778 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"a997778\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-d0f7877 jltma-glass-effect-no\" data-id=\"d0f7877\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-b7a6a59 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"b7a6a59\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/Compound-2E-q2m4osunns0djt9yybv9vyey2fm02aey4133wlnk70.jpg\" title=\"Compound 2E\" alt=\"Compound 2E\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Compound 2E<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-2b3e2ae elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"2b3e2ae\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-9c5ff79 jltma-glass-effect-no\" data-id=\"9c5ff79\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5f442fd jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"5f442fd\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>Compound 2E: <\/strong>This pyrazolo[3,4-<em>d<\/em>]pyridazinone was reported a covalent FGFR inhibitor, targeting Cys488 using a canonical acrylamide electrophile (and a 1,4-conjugate addition mechanism). There are 5 isoforms of FGFR (FGFR1, FGFR2, FGFR3, FGFR4, and FGFRL1, which have been extensively studied as oncology targets. Lead optimization towards compound 2E involved structure-based strategies and molecular docking studies (PDB 3TT0). Against FGFR1, FGFR2, FGFR3, an \u00adIC<sub>50<\/sub> of 24.1, 13.6 and 52.6 nM was found. In a FGFR2-N549H study an IC<sub>50<\/sub> of 16 nM was reported, and in SNU-16\/H716 assays, IC<sub>50<\/sub> values of 1.2\/3.2 nM were found. <em>In vivo<\/em> efficacy was established in 3 FGFR xenograft models, at 200 mg\/kg (p.o.), with TGI percentages ranging between 68-83%.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01507\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1021\/acs.jmedchem.2c01507<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-4dc8a65 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"4dc8a65\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-f8dac43 jltma-glass-effect-no\" data-id=\"f8dac43\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4dad51f jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"4dad51f\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>PF-07258669<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-71f53cf elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"71f53cf\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-3378d2e jltma-glass-effect-no\" data-id=\"3378d2e\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-d069512 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"d069512\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/PF-07258669-q2m4otshum1nvf8lsu9wgg6enthd9ziog5qldvm60s.jpg\" title=\"PF-07258669\" alt=\"PF-07258669\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">PF-07258669<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-fb9fcda elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"fb9fcda\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-f2022ed jltma-glass-effect-no\" data-id=\"f2022ed\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-dc35d5a jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"dc35d5a\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>PF-07258669: <\/strong>This spirocyclic structure out of Pfizer, has been reported as a melanocortin-4 receptor (MC4R) antagonist. MC4R is a GPCR implicated in hyperphagia, anorexia, and cachexia (related to food intake, appetite, weight loss, etc.). Using a screen of 28K analogs, and a structural mechanistic observation of an acyl migration, a series of 1-acylaminopyrrolidines was discovered. Against <em>h<\/em>MC4R, an IC<sub>50<\/sub> of 13 nM was found, with a K<sub>i<\/sub> of 0.46 nM. <em>In vivo<\/em> PK studies in rats, at 5 mg\/kg (p.o.) revealed a T<sub>1\/2<\/sub> of 0.98 hrs, a T<sub>Max<\/sub> of 0.5 hrs and an oral bioavailability (% F) of 28%. In relevant animal models of anorexia\/cachexia, at 10 mg\/kg (BID), a +111% increase of food intake was observed after the administration of this compound.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1021\/acs.jmedchem.2c02012\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1021\/acs.jmedchem.2c02012<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-b65e521 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"b65e521\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-05c8071 jltma-glass-effect-no\" data-id=\"05c8071\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-3e2cd31 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"3e2cd31\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-8a703aa elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"8a703aa\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-44a6b10 jltma-glass-effect-no\" data-id=\"44a6b10\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-d25d3a3 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"d25d3a3\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><h2><strong>MH3<\/strong><\/h2><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-9855fbf elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"9855fbf\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-8674442 jltma-glass-effect-no\" data-id=\"8674442\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-dfe0038 jltma-glass-effect-no elementor-widget elementor-widget-image\" data-id=\"dfe0038\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" src=\"https:\/\/dalriadatx.com\/wp-content\/uploads\/elementor\/thumbs\/MH3-q2m4ouqc1g2y7178ncoj0xxv97cqhomesae2v5kruk.jpg\" title=\"MH3\" alt=\"MH3\" loading=\"lazy\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">MH3<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-bf1318b elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"bf1318b\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-b07f0ec jltma-glass-effect-no\" data-id=\"b07f0ec\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-25d1145 jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"25d1145\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<section class=\"has_ma_el_bg_slider elementor-section elementor-top-section elementor-element elementor-element-691f658 elementor-section-boxed elementor-section-height-default elementor-section-height-default jltma-glass-effect-no\" data-id=\"691f658\" data-element_type=\"section\"><div class=\"elementor-container elementor-column-gap-default\"><div class=\"has_ma_el_bg_slider elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-ff9c429 jltma-glass-effect-no\" data-id=\"ff9c429\" data-element_type=\"column\"><div class=\"elementor-widget-wrap elementor-element-populated\"><div class=\"elementor-element elementor-element-fcb040d jltma-glass-effect-no elementor-widget elementor-widget-text-editor\" data-id=\"fcb040d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\"><div class=\"elementor-widget-container\"><p><strong>MH3: <\/strong>This (<em>R)<\/em>-3-aminopyrrolidine has been reported as an inhibitor of Melanin Concentrating Hormone (MCH-R1). This GPCR has been also implicated in food intake, weight loss, and appetite circuits. Using a structure-based strategy, and molecular docking, key interactions were predicted with Phe282, Trp248, Asp192, and Gln196. Using a SWISS ADME Boiled-egg model, permeation into the blood-brain-barrier has been predicted. In a radio-ligand binding assay CHO (I<sup>125<\/sup>-MCH-R1), a K<sub>i<\/sub> value of 7 nM was reported.<\/p><p><strong>Reference: <\/strong><a href=\"https:\/\/doi.org\/10.1016\/j.bmcl.2023.129194\" target=\"_blank\" rel=\"noopener\"><strong>https:\/\/doi.org\/10.1016\/j.bmcl.2023.129194<\/strong><\/a><\/p><\/div><\/div><\/div><\/div><\/div><\/section>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>The following list of 9 molecules, out of various drug discovery journals, have been primarily identified through the use of structure-based drug design strategies (SBDD), including X-ray co-crystal analysis, molecular modelling, receptor-ligand docking, and large-scales virtual screens. Altogether, these compounds have been designed to bind a diverse set of targets, including proteosome \u03b25, CES Notum, [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":6432,"menu_order":0,"template":"","format":"standard","articles_folder":[],"_links":{"self":[{"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/articles\/6438"}],"collection":[{"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/articles"}],"about":[{"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/types\/articles"}],"author":[{"embeddable":true,"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/users\/2"}],"version-history":[{"count":4,"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/articles\/6438\/revisions"}],"predecessor-version":[{"id":7293,"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/articles\/6438\/revisions\/7293"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/media\/6432"}],"wp:attachment":[{"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/media?parent=6438"}],"wp:term":[{"taxonomy":"articles_folder","embeddable":true,"href":"https:\/\/dalriadatx.com\/wp-json\/wp\/v2\/articles_folder?post=6438"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}