{"id":3922,"date":"2025-01-20T15:25:50","date_gmt":"2025-01-20T15:25:50","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=3922"},"modified":"2026-04-30T12:08:53","modified_gmt":"2026-04-30T11:08:53","slug":"refinement-of-the-bump-and-hole-approach","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2025\/01\/20\/refinement-of-the-bump-and-hole-approach\/","title":{"rendered":"Refinement of the \u201cBump-and-Hole\u201d Approach"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Well done for this tour-de-force study to our BBSRC EastBio PhD student&nbsp;Andrew, to Kwok-Ho, Andrea, and to former Lab members Michael, Lars and Matt -with important contributions from our collaborators too!<\/p>\n\n\n\n<figure class=\"wp-block-gallery has-nested-images columns-3 is-cropped wp-block-gallery-1 is-layout-flex wp-block-gallery-is-layout-flex\">\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/Abstract-ChemSci-ac.png\"><img loading=\"lazy\" decoding=\"async\" width=\"939\" height=\"471\" data-id=\"3923\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/Abstract-ChemSci-ac.png\" alt=\"ToC Graphics\" class=\"wp-image-3923\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f2_hi-res.jpg\"><img decoding=\"async\" data-id=\"3932\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f2_hi-res-898x1024.jpg\" alt=\"Fig. 2 L\/V mutant characterization\" class=\"wp-image-3932\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-s1_hi-res.jpg\"><img decoding=\"async\" data-id=\"3931\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-s1_hi-res-1024x925.jpg\" alt=\"Scheme 1 Bumped compound synthesis\" class=\"wp-image-3931\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f1_hi-res.jpg\"><img decoding=\"async\" data-id=\"3933\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f1_hi-res-478x1024.jpg\" alt=\"Fig. 1 Bump-&amp;-hole system optimization\" class=\"wp-image-3933\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f3_hi-res.jpg\"><img decoding=\"async\" data-id=\"3930\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f3_hi-res-904x1024.jpg\" alt=\"&quot;Fig. 3 Compound modifications &amp; BRD:ligand co-crystal structures.\" class=\"wp-image-3930\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f4_hi-res.jpg\"><img decoding=\"async\" data-id=\"3929\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f4_hi-res-722x1024.jpg\" alt=\"Fig. 4 Bumped compounds can inhibit single bromodomains and are effective in cells\" class=\"wp-image-3929\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f5_hi-res.jpg\"><img decoding=\"async\" data-id=\"3928\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f5_hi-res-628x1024.jpg\" alt=\"Fig. 5 Enantiomer Characterization\" class=\"wp-image-3928\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f6_hi-res.jpg\"><img decoding=\"async\" data-id=\"3927\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f6_hi-res-1024x814.jpg\" alt=\"Fig. 6 (2R,3S)-7: a potent and highly-selective bumped BET inhibitor\" class=\"wp-image-3927\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f7_hi-res.jpg\"><img decoding=\"async\" data-id=\"3926\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f7_hi-res-654x1024.jpg\" alt=\"Fig. 7 (2R,3S)-7 does not perturb WT BET-dependent cells.\" class=\"wp-image-3926\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f8_hi-res.jpg\"><img decoding=\"async\" data-id=\"3925\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f8_hi-res-864x1024.jpg\" alt=\"Fig. 8 Application of the bump-&amp;-hole system to a biological question\" class=\"wp-image-3925\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f9_hi-res.jpg\"><img decoding=\"async\" data-id=\"3924\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f9_hi-res-678x1024.jpg\" alt=\"Fig. 9 BRD4 and NF-\u03baB-target gene expression\" class=\"wp-image-3924\"\/><\/a><\/figure>\n<\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">Well done for this tour-de-force study to our BBSRC EastBio PhD student&nbsp;Andrew, to Kwok-Ho, Andrea, and to former Lab members Michael, Lars and Matt -with important contributions from our collaborators too!<\/p>\n\n\n\n<figure class=\"wp-block-gallery has-nested-images columns-3 is-cropped wp-block-gallery-2 is-layout-flex wp-block-gallery-is-layout-flex\">\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/Abstract-ChemSci-ac.png\"><img loading=\"lazy\" decoding=\"async\" width=\"939\" height=\"471\" data-id=\"3923\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/Abstract-ChemSci-ac.png\" alt=\"ToC Graphics\" class=\"wp-image-3923\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f2_hi-res.jpg\"><img decoding=\"async\" data-id=\"3932\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f2_hi-res-898x1024.jpg\" alt=\"Fig. 2 L\/V mutant characterization\" class=\"wp-image-3932\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-s1_hi-res.jpg\"><img decoding=\"async\" data-id=\"3931\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-s1_hi-res-1024x925.jpg\" alt=\"Scheme 1 Bumped compound synthesis\" class=\"wp-image-3931\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f1_hi-res.jpg\"><img decoding=\"async\" data-id=\"3933\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f1_hi-res-478x1024.jpg\" alt=\"Fig. 1 Bump-&amp;-hole system optimization\" class=\"wp-image-3933\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f3_hi-res.jpg\"><img decoding=\"async\" data-id=\"3930\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f3_hi-res-904x1024.jpg\" alt=\"&quot;Fig. 3 Compound modifications &amp; BRD:ligand co-crystal structures.\" class=\"wp-image-3930\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f4_hi-res.jpg\"><img decoding=\"async\" data-id=\"3929\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f4_hi-res-722x1024.jpg\" alt=\"Fig. 4 Bumped compounds can inhibit single bromodomains and are effective in cells\" class=\"wp-image-3929\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f5_hi-res.jpg\"><img decoding=\"async\" data-id=\"3928\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f5_hi-res-628x1024.jpg\" alt=\"Fig. 5 Enantiomer Characterization\" class=\"wp-image-3928\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f6_hi-res.jpg\"><img decoding=\"async\" data-id=\"3927\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f6_hi-res-1024x814.jpg\" alt=\"Fig. 6 (2R,3S)-7: a potent and highly-selective bumped BET inhibitor\" class=\"wp-image-3927\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f7_hi-res.jpg\"><img decoding=\"async\" data-id=\"3926\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f7_hi-res-654x1024.jpg\" alt=\"Fig. 7 (2R,3S)-7 does not perturb WT BET-dependent cells.\" class=\"wp-image-3926\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f8_hi-res.jpg\"><img decoding=\"async\" data-id=\"3925\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f8_hi-res-864x1024.jpg\" alt=\"Fig. 8 Application of the bump-&amp;-hole system to a biological question\" class=\"wp-image-3925\"\/><\/a><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f9_hi-res.jpg\"><img decoding=\"async\" data-id=\"3924\" src=\"https:\/\/sites.dundee.ac.uk\/wp-content\/uploads\/sites\/233\/2025\/01\/c7sc02536j-f9_hi-res-678x1024.jpg\" alt=\"Fig. 9 BRD4 and NF-\u03baB-target gene expression\" class=\"wp-image-3924\"\/><\/a><\/figure>\n<\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Well done for this tour-de-force study to our BBSRC EastBio PhD student&nbsp;Andrew, to Kwok-Ho, Andrea, and to former Lab members Michael, Lars and Matt -with important contributions from our collaborators too! Well done for this tour-de-force study to our BBSRC EastBio PhD student&nbsp;Andrew, to Kwok-Ho, Andrea, and to former Lab members Michael, Lars and Matt [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[],"class_list":["post-3922","post","type-post","status-publish","format-standard","hentry","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/3922","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=3922"}],"version-history":[{"count":4,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/3922\/revisions"}],"predecessor-version":[{"id":4893,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/3922\/revisions\/4893"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=3922"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=3922"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=3922"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}