{"id":2416,"date":"2019-02-22T15:07:00","date_gmt":"2019-02-22T15:07:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2416"},"modified":"2026-01-26T16:28:04","modified_gmt":"2026-01-26T16:28:04","slug":"crbn-versus-vhl","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2019\/02\/22\/crbn-versus-vhl\/","title":{"rendered":"CRBN versus VHL"},"content":{"rendered":"<p>Our new PROTAC paper on hijacking E3 ligases against each others is now published in Bioorg. Med. Chem.<\/p>\n<p><a href=\"https:\/\/doi.org\/10.1016\/j.bmc.2019.02.048\">Read the full paper Open Access<\/a>.<\/p>\n<p>Well done Miriam, Chiara, Scott and Andrea on this work!<\/p>\n<div id='gallery-1' class='gallery galleryid-2416 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\/ToC-CRBN-VHL-revised-01-2.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"729\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-1024x729.jpg\" class=\"attachment-large size-large\" alt=\"ToC Graphic for CRBN VHL\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-1024x729.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-300x214.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-768x547.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-1536x1094.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/ToC-CRBN-VHL-revised-01-2-2048x1459.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-2.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"895\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2-1024x895.jpg\" class=\"attachment-large size-large\" alt=\"Figure 1. Previously published homo-PROTACs CM11 and CC15a, which induce self-degradation of the E3 ligases VHL and CRBN, respectively\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2-1024x895.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2-300x262.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2-768x672.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2-1536x1343.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-2.jpg 1673w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-fig02.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"664\" height=\"1024\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-664x1024.jpg\" class=\"attachment-large size-large\" alt=\"Figure 2. Design of VHL-CRBN conjugates explored in this work\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-664x1024.jpg 664w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-194x300.jpg 194w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-768x1185.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-996x1536.jpg 996w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02-1328x2048.jpg 1328w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig02.jpg 1673w\" sizes=\"auto, (max-width: 664px) 100vw, 664px\" \/><\/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\/CRBN-VHL-fig03.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"563\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03-1024x563.jpg\" class=\"attachment-large size-large\" alt=\"Figure 3. Chemical structure of VHL ligands 1 and 2, and CRBN ligand 3\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03-1024x563.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03-300x165.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03-768x422.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03-1536x845.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig03.jpg 1673w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-scheme01.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"216\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-1024x216.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 1. Synthesis of PROTACs 7a-b\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-1024x216.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-300x63.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-768x162.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-1536x324.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme01-2048x432.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-scheme02.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"770\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-1024x770.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 2. Synthesis of PROTACs 14a-e\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-1024x770.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-300x226.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-768x578.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-1536x1155.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme02-2048x1540.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-scheme03.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"490\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-1024x490.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 3. Synthesis of PROTACs 18a-c\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-1024x490.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-300x144.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-768x368.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-1536x735.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme03-2048x980.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-scheme04.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"601\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-1024x601.jpg\" class=\"attachment-large size-large\" alt=\"Scheme 4. Synthesis of PROTACs 22a-c\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-1024x601.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-300x176.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-768x451.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-1536x902.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-scheme04-2048x1202.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-fig04.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"552\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig04-1024x552.jpg\" class=\"attachment-large size-large\" alt=\"Figure 4. Screening of VHL-CRBN hetero-PROTACs\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig04-1024x552.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig04-300x162.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig04-768x414.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig04.jpg 1193w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/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\/CRBN-VHL-fig05.jpg'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"859\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-1024x859.jpg\" class=\"attachment-large size-large\" alt=\"Figure 5. Compound 14a induces rapid depletion of CRBN, but not of VHL\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-1024x859.jpg 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-300x252.jpg 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-768x644.jpg 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-1536x1289.jpg 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/CRBN-VHL-fig05-2048x1718.jpg 2048w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a>\n\t\t\t<\/div><\/figure>\n\t\t<\/div>\n\n","protected":false},"excerpt":{"rendered":"<p>Our new PROTAC paper on hijacking E3 ligases against each others is now published in Bioorg. Med. Chem. Read the full paper Open Access. Well done Miriam, Chiara, Scott and Andrea on this work!<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[17,4],"tags":[],"class_list":["post-2416","post","type-post","status-publish","format-standard","hentry","category-17","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2416","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=2416"}],"version-history":[{"count":2,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2416\/revisions"}],"predecessor-version":[{"id":4865,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2416\/revisions\/4865"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2416"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2416"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2416"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}