{"id":2057,"date":"2026-05-07T16:56:56","date_gmt":"2026-05-07T14:56:56","guid":{"rendered":"https:\/\/sites.unica.it\/pe2026\/?p=2057"},"modified":"2026-05-08T17:21:30","modified_gmt":"2026-05-08T15:21:30","slug":"chaimae-el-hadri","status":"publish","type":"post","link":"https:\/\/sites.unica.it\/pe2026\/2026\/05\/07\/chaimae-el-hadri\/","title":{"rendered":"Chaimae El Hadri"},"content":{"rendered":"\n
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PC9 – Chaimae El Hadri<\/strong><\/p>\n\n\n\n

Ghent University, Ghent, Belgium<\/p>\n\n\n\n

chaimae.elhadri@ugent.be<\/strong><\/p>\n<\/div><\/div>\n\n\n\n

Targeting CtBP Mediated Oncogenic Transcriptional Activity With Structure Guided Ligand<\/em><\/strong><\/td><\/tr>
El Hadri Chaimae1,2,4<\/sup>, DeBacker Robin3,4<\/sup>, Savvas Savvides3,4<\/sup>, Steven Goossens1,4<\/sup>, Serge Van Calenbergh2,4<\/sup><\/em>

1<\/sup><\/em> Unit for Translational Research in Oncology (UTRiO), Ghent University, Ghent, Belgium
2<\/sup><\/em> Laboratory for Medicinal Chemistry, Ghent University, Ghent, Belgiuma
3<\/sup><\/em> Unit for Structural Biology, VIB Ghent University, Ghent, Belgium
4<\/sup><\/em> Cancer Research Institute Ghent (CRIG), Ghent, Belgium<\/td><\/tr>
Abstract<\/strong>
C-terminal Binding Proteins (CtBP1\/2) are NADH-dependent transcriptional corepressors frequently overexpressed in cancer, where they drive epithelial mesenchymal transition (EMT) and repress tumor suppressor programs (CDH1, BRCA1)[1-2]. However, the interplay between their catalytic activity, oligomerization, and transcriptional function remains poorly understood. Here, we report the structure guided development of new CtBP inhibitors derived from 2-hydroxyimino 3-phenylpropanoic acid (HIPP)[3]. The most potent compounds display nanomolar inhibition of CtBP dehydrogenase activity (IC\u2085\u2080 \u2248 20 nM). Biophysical and structural studies (thermal shift, ITC, and X-ray crystallography) reveal high affinity binding and show that the enzymatic inhibition is coupled to perturbation of CtBP oligomerization, a key determinant of its transcriptional activity. In breast and ovarian cancer models, the ethyl esters of these compounds reduce viability (IC\u2085\u2080 \u2248 15 \u00b5M) and induce transcriptional reprogramming consistent with CtBP modulation.  These results provide insight into the relationship between CtBP catalytic activity and transcriptional regulation, and support further exploration of CtBP as a therapeutic target.<\/td><\/tr>
References  <\/strong>
[1] Deng, Y.; et al. Transcriptional Down-Regulation of Brca1 and E-Cadherin by CtBP1 in Breast Cancer. Mol. Carcinog. 2012, 51, 500\u2013507.
[2] Blevins, M. A.; Huang, M.; Zhao, R. The Role of CtBP1 in Oncogenic Processes and Its Potential as a Therapeutic Target. Mol. Cancer Ther. 2017, 16, 981\u2013990.
[3] Hilbert, B. J.; et al. Structure-Guided Design of a High Affinity Inhibitor to Human CtBP. ACS Chem. Biol. 2015, 10, 1118\u20131127.<\/td><\/tr><\/tbody><\/table><\/div><\/figure>\n","protected":false},"excerpt":{"rendered":"

PC9 – Chaimae El Hadri Ghent University, Ghent, Belgium chaimae.elhadri@ugent.be Targeting CtBP Mediated Oncogenic Transcriptional Activity With Structure Guided Ligand El Hadri Chaimae1,2,4, DeBacker Robin3,4, Savvas Savvides3,4, Steven Goossens1,4, Serge Van Calenbergh2,4 1 Unit for Translational […]<\/p>\n","protected":false},"author":10371,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-2057","post","type-post","status-publish","format-standard","hentry","category-senza-categoria"],"_links":{"self":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2057","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/users\/10371"}],"replies":[{"embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/comments?post=2057"}],"version-history":[{"count":3,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2057\/revisions"}],"predecessor-version":[{"id":2334,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/posts\/2057\/revisions\/2334"}],"wp:attachment":[{"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/media?parent=2057"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/categories?post=2057"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sites.unica.it\/pe2026\/wp-json\/wp\/v2\/tags?post=2057"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}