دورية أكاديمية
Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site
| العنوان: | Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site |
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| المؤلفون: | Masini, Tiziana, Birkaya, Barbara, van Dijk, Simon, Mondal, Milon, Hekelaar, Johan, Jager, Manuel, van Scheltinga, Anke C. Terwisscha, Patel, Mulchand S., Hirsch, Anna K. H., Moman, Edelmiro |
| المصدر: | Masini , T , Birkaya , B , van Dijk , S , Mondal , M , Hekelaar , J , Jager , M , van Scheltinga , A C T , Patel , M S , Hirsch , A K H & Moman , E 2016 , ' Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site ' , Journal of enzyme inhibition and medicinal chemistry , vol. 31 (S4) , pp. 170-175 . https://doi.org/10.1080/14756366.2016.1201812Test |
| سنة النشر: | 2016 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Cancer metabolism, DCA, dichloroacetate, PDC, PDK2 inhibitors, pyruvate, CANCER-CELLS, METABOLISM, MECHANISMS, PHOSPHORYLATION, HYPOXIA, COMPLEX |
| الوصف: | The last decade has witnessed the reawakening of cancer metabolism as a therapeutic target. In particular, inhibition of pyruvate dehydrogenase kinase (PDK) holds remarkable promise. Dichloroacetic acid (DCA), currently undergoing clinical trials, is a unique PDK inhibitor in which it binds to the allosteric pyruvate site of the enzyme. However, the safety of DCA as a drug is compromised by its neurotoxicity, whereas its usefulness as an investigative tool is limited by the high concentrations required to exert observable effects in cell culture. Herein, we report the identification - by making use of saturation-transfer difference NMR spectroscopy, enzymatic assays and computational methods - of furoate and thenoate derivatives as allosteric pyruvate-site-binding PDK2 inhibitors. This work substantiates the pyruvate regulatory pocket as a druggable target. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/76919835-c6d6-43a6-a56d-90c7f9175723Test |
| DOI: | 10.1080/14756366.2016.1201812 |
| الإتاحة: | https://doi.org/10.1080/14756366.2016.1201812Test https://hdl.handle.net/11370/76919835-c6d6-43a6-a56d-90c7f9175723Test https://research.rug.nl/en/publications/76919835-c6d6-43a6-a56d-90c7f9175723Test https://pure.rug.nl/ws/files/78980585/Furoates_and_thenoates_inhibit_pyruvate_dehydrogenase_kinase_2_allosterically_by_binding.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7A853434 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1080/14756366.2016.1201812 |
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