{"id":13310,"date":"2025-10-08T11:26:45","date_gmt":"2025-10-08T10:26:45","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=13310"},"modified":"2025-10-15T11:46:24","modified_gmt":"2025-10-15T10:46:24","slug":"fragment-to-lead-successes-in-2023","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2025\/10\/fragment-to-lead-successes-in-2023\/","title":{"rendered":"Fragment-to-Lead Successes in 2023"},"content":{"rendered":"\n<p>Back in 2021, I highlighted the annual fragment-to-lead (F2L) success stories from 2019 <a href=\"https:\/\/www.blopig.com\/blog\/2021\/01\/fragment-to-lead-successes-in-2019\/\">[Blog post]<\/a> <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jmedchem.0c01608\">[Paper]<\/a>. This is one of my favourite annual publications, and I&#8217;m delighted to see that it&#8217;s still going strong. In this post, I&#8217;ll discuss the 2023 edition that was published in at the start of 2025 <a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.jmedchem.4c02593\">[Paper]<\/a>.<\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?ssl=1\"><img data-recalc-dims=\"1\" decoding=\"async\" width=\"625\" height=\"353\" loading=\"lazy\" src=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?resize=625%2C353&#038;ssl=1\" alt=\"\" class=\"wp-image-13311\" srcset=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?w=994&amp;ssl=1 994w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?resize=300%2C170&amp;ssl=1 300w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?resize=768%2C434&amp;ssl=1 768w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2025\/10\/fragment_to_lead_2023.png?resize=624%2C353&amp;ssl=1 624w\" sizes=\"auto, (max-width: 625px) 100vw, 625px\" \/><\/a><\/figure>\n\n\n\n<!--more-->\n\n\n\n<p><strong>17 entries drawn from 16 papers<\/strong> met the F2L bar for 2023 (clear fragment hits, structure\/biophysics to confirm binding, and optimisation to potent leads). This is broadly steady with recent years.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">What\u2019s (still) working<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Structure-first FBDD<\/strong> continues to dominate: crystallography underpins many campaigns, with orthogonal biophysics the default.<\/li>\n\n\n\n<li><strong>All main development strategies (growing\/merging\/linking)<\/strong> are represented. While the majority of F2L examples employ growing or merging, there are some interesting linking examples this year.<\/li>\n\n\n\n<li><strong>Continued focus on lead efficiency<\/strong>: while a number of papers highighted ways of speeding up the elaboration process, there remains a high focus on ensuring elaboration are efficient (e.g. as measured by ligand efficiency (LE), ligand lipophilicity efficiency (LLE)). <\/li>\n<\/ul>\n\n\n\n<h2 class=\"wp-block-heading\">What felt new\/more prominent in 2023<\/h2>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>NMR and virtual screening<\/strong> received special mention. Historically fragment-based drug discovery has been relatively unimpacted by computational work compared to other areas so it was great to see this and&#8230;<\/li>\n\n\n\n<li><strong>OPIG tool Fragmenstein<\/strong> <a href=\"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/s13321-025-00946-0\">[Paper]<\/a> for fragment merging was highlighed prominently.<\/li>\n\n\n\n<li><strong>Library design<\/strong> continues to evolve (more diverse, 3D-rich, functionally ready fragments), feeding rapid expansion\/optimisation.<\/li>\n<\/ul>\n\n\n\n<p>Overall, it feels as if the field has continued to mature: output has remained steady, with improved experimental tooling and computational techniques.<\/p>\n\n\n\n<p>If you&#8217;re interested in FBDD, <a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.jmedchem.4c02593\">take a look!<\/a><\/p>\n\n\n\n<p>Citation: Holvey, R. S., Erlanson, D. A., de Esch, I. J., Farkas, B., Jahnke, W., Nishiyama, T., &amp; Woodhead, A. J. (2025). Fragment-to-lead medicinal chemistry publications in 2023.&nbsp;<em>Journal of medicinal chemistry<\/em>,&nbsp;<em>68<\/em>(2), 986-1001.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><\/li>\n<\/ul>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Back in 2021, I highlighted the annual fragment-to-lead (F2L) success stories from 2019 [Blog post] [Paper]. This is one of my favourite annual publications, and I&#8217;m delighted to see that it&#8217;s still going strong. In this post, I&#8217;ll discuss the 2023 edition that was published in at the start of 2025 [Paper].<\/p>\n","protected":false},"author":50,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","wikipediapreview_detectlinks":true,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"ngg_post_thumbnail":0,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[187,138,447,48,201],"tags":[118,477,102],"ppma_author":[535],"class_list":["post-13310","post","type-post","status-publish","format-standard","hentry","category-cheminformatics","category-journal-club","category-molecular-design","category-publication","category-small-molecules","tag-drug-discovery","tag-fragment-based-drug-discovery","tag-fragments"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"authors":[{"term_id":535,"user_id":50,"is_guest":0,"slug":"fergus2","display_name":"Fergus Imrie","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/19c18fa7f4d0a2aecc5f69760c6a9f2fc9b493dfe45b1fd333ccb447db9d6a90?s=96&d=mm&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/13310","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/users\/50"}],"replies":[{"embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/comments?post=13310"}],"version-history":[{"count":3,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/13310\/revisions"}],"predecessor-version":[{"id":13356,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/13310\/revisions\/13356"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=13310"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=13310"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=13310"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=13310"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}