{"id":14039,"date":"2026-03-24T16:39:10","date_gmt":"2026-03-24T16:39:10","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=14039"},"modified":"2026-03-24T16:39:15","modified_gmt":"2026-03-24T16:39:15","slug":"fragment-to-lead-successes-in-2024-10th-anniversary-edition","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2026\/03\/fragment-to-lead-successes-in-2024-10th-anniversary-edition\/","title":{"rendered":"Fragment-to-Lead Successes in 2024 &#8211; 10th Anniversary Edition"},"content":{"rendered":"\n<figure class=\"wp-block-image size-full\"><a href=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2026\/03\/F2L_2024.png?ssl=1\"><img decoding=\"async\" width=\"692\" height=\"478\" loading=\"lazy\" src=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2026\/03\/F2L_2024.png?fit=692%2C478&amp;ssl=1\" alt=\"\" class=\"wp-image-14041\" srcset=\"https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2026\/03\/F2L_2024.png?w=692&amp;ssl=1 692w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2026\/03\/F2L_2024.png?resize=300%2C207&amp;ssl=1 300w, https:\/\/i0.wp.com\/www.blopig.com\/blog\/wp-content\/uploads\/2026\/03\/F2L_2024.png?resize=624%2C431&amp;ssl=1 624w\" sizes=\"auto, (max-width: 625px) 100vw, 625px\" \/><\/a><\/figure>\n\n\n\n<p class=\"wp-block-paragraph\">In what I have to admit is now becoming an annual tradition (<a href=\"https:\/\/www.blopig.com\/blog\/2025\/10\/fragment-to-lead-successes-in-2023\/\">[2023]<\/a> <a href=\"https:\/\/www.blopig.com\/blog\/2021\/01\/fragment-to-lead-successes-in-2019\/\">[2019]<\/a>), I&#8217;d like to highlight the 2024 edition of the fragment-to-lead success stories, published in J. Med. Chem. at the end of 2025 <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jmedchem.5c02894\">[Paper]<\/a>.<\/p>\n\n\n\n<!--more-->\n\n\n\n<p class=\"wp-block-paragraph\">This year&#8217;s publication covers <strong>18 case studies<\/strong> (in line with last year&#8217;s 17, but lower than the 10-year average), for a cumulative <strong>233 examples since 2015<\/strong>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>New\/On-the-up in 2024<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"\"><strong>Membrane proteins: <\/strong>Multiple publications covered efforts to screen membrane proteins with fragments, typically a challenging target class for X-ray crystallography.<\/li>\n\n\n\n<li class=\"\"><strong>New ligand modalities:<\/strong> Fragments are being used to design PROTACs and molecular glues.<\/li>\n\n\n\n<li class=\"\"><strong>&#8220;Covalent first&#8221;:<\/strong> While developing covalent binders from fragment screens isn&#8217;t new, the recent surge in screening covalently reactive compounds to identify hit matter, rather than introducing a reactive warhead to a noncovalent starting point, continued.<\/li>\n\n\n\n<li class=\"\"><strong>Computational methods: <\/strong>While only one virtual screen was reported, most F2L stories included computational design aspects, including one case where FEP was used extensively in the optimisation process.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Key Challenges<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li class=\"\"><strong>Progressing hits: <\/strong>The authors noted the increasing number of fragment screens being reported with limited\/no development of those hits. This is a critical step for which we need more robust, reliable techniques.  <\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Finally, it was great to see the XChem facility at Diamond Light Source be explicitly mentioned. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Citation:<\/strong> Twigg, D.G., Arai, K., Arkin, M.R., Erlanson, D.A., de Esch, I.J., Farka\u0161, B., Fesik, S.W., Jahnke, W., Johnson, C.N. and Schroeder, M., 2025. Fragment-to-Lead Medicinal Chemistry Publications in 2024: A Tenth Annual Perspective. <em>Journal of Medicinal Chemistry<\/em>, <em>68<\/em>(23), 24830-24847.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>In what I have to admit is now becoming an annual tradition ([2023] [2019]), I&#8217;d like to highlight the 2024 edition of the fragment-to-lead success stories, published in J. Med. Chem. at the end 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-14039","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\/14039","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=14039"}],"version-history":[{"count":1,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/14039\/revisions"}],"predecessor-version":[{"id":14042,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/posts\/14039\/revisions\/14042"}],"wp:attachment":[{"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/media?parent=14039"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/categories?post=14039"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/tags?post=14039"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.blopig.com\/blog\/wp-json\/wp\/v2\/ppma_author?post=14039"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}