{"id":2799,"date":"2014-10-16T08:10:00","date_gmt":"2014-10-16T07:10:00","guid":{"rendered":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/?p=2799"},"modified":"2026-01-26T16:28:06","modified_gmt":"2026-01-26T16:28:06","slug":"chemical-genetics-bump-and-hole-approach-to-engineer-controlled-selectivity-of-bet-bromodomain-inhibitors","status":"publish","type":"post","link":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/2014\/10\/16\/chemical-genetics-bump-and-hole-approach-to-engineer-controlled-selectivity-of-bet-bromodomain-inhibitors\/","title":{"rendered":"Chemical genetics bump-and-hole approach\u00a0to engineer controlled selectivity of BET bromodomain inhibitors"},"content":{"rendered":"<p>Just published in Science! Our paper describing a chemical genetics bump-and-hole approach to engineer controlled selectivity of BET bromodomain inhibitors.<\/p>\n<ul>\n<li><a href=\"http:\/\/europepmc.org\/articles\/PMC4458378;jsessionid=ClO0BRg23y1H3xvmc0EC.0\">Read our paper open-access in Europe PMC\u00a0<\/a><\/li>\n<li>Highlighted in the\u00a0<a href=\"http:\/\/www.bbsrc.ac.uk\/news\/health\/2014\/141020-pr-bump-and-hole-brings-protein-breakthrough.aspx\">BBSRC<\/a>\u00a0website<\/li>\n<li>Highlighted in\u00a0<a href=\"http:\/\/dx.doi.org\/10.1158\/2159-8290.CD-RW2014-222\">Cancer Discovery Research Watch<\/a>.<\/li>\n<li>Highlighted in\u00a0<a href=\"http:\/\/www.nature.com\/nchembio\/journal\/v10\/n12\/full\/nchembio.1706.html\">Nature Chemical Biology<\/a><\/li>\n<li>Highlighted in\u00a0<a href=\"http:\/\/www.nature.com\/nmeth\/journal\/v12\/n1\/full\/nmeth.3246.html\">Nature Methods<\/a><\/li>\n<\/ul>\n<div id='gallery-1' class='gallery galleryid-2799 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\/chemical-genetic-bump-fig4-Baud4transrev1.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"335\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig4-Baud4transrev1-1024x335.png\" class=\"attachment-large size-large\" alt=\"Figure 4. ET is highly selective for Leu\/Ala BET bromodomains in vitro and in cells\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig4-Baud4transrev1-1024x335.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig4-Baud4transrev1-300x98.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig4-Baud4transrev1-768x251.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig4-Baud4transrev1.png 1414w\" 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\/chemical-genetic-bump-fig3-1249830fig3.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"760\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-1024x760.png\" class=\"attachment-large size-large\" alt=\"Figure 3. Bumped ligand ET binds to engineered Leu\/Ala bromodomains with high selectivity\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-1024x760.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-300x223.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-768x570.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-1536x1140.png 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig3-1249830fig3-2048x1519.png 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\/chemical-genetic-bump-fig2-1249830fig2.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"637\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-1024x637.png\" class=\"attachment-large size-large\" alt=\"&quot;Figure 2. Identification of Leu94 as mutational position and bumped ligand design\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-1024x637.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-300x187.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-768x478.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-1536x956.png 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig2-1249830fig2-2048x1275.png 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\/chemical-genetic-bump-fig1-1249830fig1.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"477\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-1024x477.png\" class=\"attachment-large size-large\" alt=\"Figure 1. BET bromodomains, pan-selective inhibitors and bump-and-hole approach\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-1024x477.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-300x140.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-768x358.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-1536x715.png 1536w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-fig1-1249830fig1-2048x954.png 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\/chemical-genetic-bump-hole_smaller.png'><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"683\" src=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-hole_smaller-1024x683.png\" class=\"attachment-large size-large\" alt=\"Bump-and-hole tailored selectivity of JQ1\/I-BET\" srcset=\"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-hole_smaller-1024x683.png 1024w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-hole_smaller-300x200.png 300w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-hole_smaller-768x512.png 768w, https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-content\/uploads\/sites\/233\/2024\/01\/chemical-genetic-bump-hole_smaller.png 1200w\" 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>Just published in Science! Our paper describing a chemical genetics bump-and-hole approach to engineer controlled selectivity of BET bromodomain inhibitors. Read our paper open-access in Europe PMC\u00a0 Highlighted in the\u00a0BBSRC\u00a0website Highlighted in\u00a0Cancer Discovery Research Watch. Highlighted in\u00a0Nature Chemical Biology Highlighted in\u00a0Nature Methods<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[22,4],"tags":[],"class_list":["post-2799","post","type-post","status-publish","format-standard","hentry","category-22","category-news"],"blocksy_meta":[],"_links":{"self":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2799","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=2799"}],"version-history":[{"count":2,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2799\/revisions"}],"predecessor-version":[{"id":4885,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/posts\/2799\/revisions\/4885"}],"wp:attachment":[{"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/media?parent=2799"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/categories?post=2799"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.dundee.ac.uk\/alessio-ciulli\/wp-json\/wp\/v2\/tags?post=2799"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}