{"id":2454,"date":"2018-12-12T16:18:00","date_gmt":"2018-12-12T16:18:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2454"},"modified":"2026-01-26T16:28:04","modified_gmt":"2026-01-26T16:28:04","slug":"a-roadmap-for-protac-development","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2018\/12\/12\/a-roadmap-for-protac-development\/","title":{"rendered":"A Roadmap for PROTAC Development"},"content":{"rendered":"<p>Our SAR story disclosing dual Brd7\/9 PROTAC degrader VZ185 is published in J. Med. Chem.<\/p>\n<p>Congratulations to\u00a0Vittoria,\u00a0Scott,\u00a0Chiara\u00a0and\u00a0Andrea, and all our collaborators for their contributions to this work!<\/p>\n<h2 class=\"wp-block-heading\">Related Links<\/h2>\n<ul>\n<li><a href=\"https:\/\/www.promegaconnections.com\/a-roadmap-for-protac-development\/\" target=\"_blank\" rel=\"noreferrer noopener\">Promega Connections blog: \u201cA Roadmap for PROTAC Development\u201d<\/a><\/li>\n<\/ul>\n<div id='gallery-1' class='gallery galleryid-2454 gallery-columns-3 gallery-size-large'><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-1-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"434\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-1-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"ToC Graphic for SAR story disclosing dual Brd7\/9 PROTAC degrader VZ185 is published in J. Med. Chem\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-2.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"986\" height=\"912\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-2.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 1. Chemical structures of parent (1a, 1b, 2\u20134) and modified (1c, 2a\u20134a) BRD7\/9 and E3 ligase ligands. Functional groups selected for conjugation are shown in blue on parent ligands and in red on modified ligands.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-3-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"493\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-3-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 1. Synthesis of the BRD7\/9 Ligand 1c\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-4-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"880\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-4-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 2. Synthesis of the First Generation of Degraders\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-5-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"381\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-5-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 2. Screening of first generation of degraders.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-6-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"195\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-6-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 3. Structures of compounds 7 and 21.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-7-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"950\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-7-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 4. Ternary complex formation and analysis of binding mode for compound 5.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-8-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"277\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-8-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 3. Synthesis of Compound 23\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-9-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"644\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-9-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 4. Synthesis of Compounds 26\u201331\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-10-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"628\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-10-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 5. Compound 26 induces rapid and profound depletion of BRD9 in cells\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-11-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"730\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-11-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 6. Improved ternary complex formation by series-2 degraders.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon portrait'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-12-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"864\" height=\"1024\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-12-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Scheme 5. General Synthetic Routes for Third-Generation Compounds\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon portrait'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-13-scaled.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"661\" height=\"1024\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-13-scaled.jpg\" class=\"attachment-large size-large\" alt=\"Figure 7. Screening of third generation of degraders\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-14-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"705\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-14-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 8. VZ185 induces strong and rapid degradation in a time- and dose-dependent manner.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-15-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"582\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-15-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 9. Quantitative live-cell kinetics of VZ185 induced degradation of BRD7 and BRD9\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-16-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"258\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-16-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 9. Quantitative live-cell kinetics of VZ185 induced degradation of BRD7 and BRD9\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-17-scaled.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"457\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-17-scaled.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 11. Effect of BRD7\/9 degradation on viability of BRD9-sensitive cancer cell lines.\" \/><\/a>\n\t\t\t<\/div><\/figure><figure class='gallery-item'>\n\t\t\t<div class='gallery-icon landscape'>\n\t\t\t\t<a href='https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-18.jpeg'><img loading=\"lazy\" decoding=\"async\" width=\"1000\" height=\"613\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/brd79-protac-18.jpeg\" class=\"attachment-large size-large\" alt=\"Figure 12. Impact of VZ185 on the cellular proteome after treatment of RI-1 cells with 100 nM compound for 4 h before harvesting.\" \/><\/a>\n\t\t\t<\/div><\/figure>\n\t\t<\/div>\n\n","protected":false},"excerpt":{"rendered":"<p>Our SAR story disclosing dual Brd7\/9 PROTAC degrader VZ185 is published in J. Med. Chem. Congratulations to\u00a0Vittoria,\u00a0Scott,\u00a0Chiara\u00a0and\u00a0Andrea, and all our collaborators for their contributions to this work! Related Links Promega Connections blog: \u201cA Roadmap for PROTAC Development\u201d<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18,4],"tags":[],"class_list":["post-2454","post","type-post","status-publish","format-standard","hentry","category-18","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2454","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/comments?post=2454"}],"version-history":[{"count":2,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2454\/revisions"}],"predecessor-version":[{"id":4867,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2454\/revisions\/4867"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2454"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2454"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2454"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}