The structure based design of dual HDAC/BET inhibitors as novel epigenetic probes
| العنوان: | The structure based design of dual HDAC/BET inhibitors as novel epigenetic probes |
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| المؤلفون: | Stephen John Atkinson, Chun-wa Chung, Peter Ernest Soden, Laurie J. Gordon, Rab K. Prinjha, Nicholas Smithers, Rebecca C. Furze, Kathryn A. Giblin, Davina C. Angell, Marcus Bantscheff, Nigel J. Parr, Inmaculada Rioja, Jason Witherington, Gerard Drewes |
| المصدر: | MedChemComm. 5:342-351 |
| بيانات النشر: | Royal Society of Chemistry (RSC), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Pharmacology, Hydroxamic acid, Organic Chemistry, Pharmaceutical Science, hemic and immune systems, chemical and pharmacologic phenomena, Biology, Biochemistry, Small molecule, In vitro, Bromodomain, chemistry.chemical_compound, chemistry, Transcription (biology), Drug Discovery, Cancer cell, Molecular Medicine, Histone deacetylase, Epigenetics |
| الوصف: | Herein we describe the design and synthesis of a dual active histone deacetylase (HDAC)/bromodomain and extra terminal (BET) small molecule tool inhibitor, DUAL946 (1). Exploiting our extensive epigenetic toolbox, we achieved the functionalisation of a BET active tetrahydroquinoline (THQ) core, with a hydroxamic acid HDAC inhibitor (HDACi) motif. Dual inhibition of BET and HDAC proteins was confirmed by in vitro biochemical and biophysical testing and through chemoproteomic competition experiments in cell lysates. This activity was translated into potent cellular activity in both immune and cancer cells. |
| تدمد: | 2040-2511 2040-2503 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3bdb6f43d6b09b952d7c8ccd1e8cfa40 https://doi.org/10.1039/c3md00285c |
| رقم الأكسشن: | edsair.doi...........3bdb6f43d6b09b952d7c8ccd1e8cfa40 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20402511 20402503 |
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