A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach
المؤلفون المشاركون
المصدر
International Journal of Medicinal Chemistry
العدد
المجلد 2014، العدد 2014 (31 ديسمبر/كانون الأول 2014)، ص ص. 1-6، 6ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2014-03-23
دولة النشر
مصر
عدد الصفحات
6
التخصصات الرئيسية
الملخص EN
Triosephosphate isomerase (TIM) is an essential, highly conserved component of glycolysis.
Tumors are often dependent on glycolysis for energy and metabolite production (the Warburg effect).
Glycolysis inhibitors thus show promise as cancer treatments.
TIM inhibition, unlike inhibition of other glycolysis enzymes, also produces toxic methylglyoxal targeted to regions of high glycolysis, an effect that might also be therapeutically useful.
Thus TIM is an attractive drug target.
A total of 338,562 lead-like molecules were analyzed computationally to find TIM inhibitors by an efficient “double screen” approach.
The first fragment-sized compounds were studied using structure-based virtual screening to identify binding motifs for mammalian TIM.
Subsequently, larger compounds, filtered to meet the binding criteria developed in the first analysis, were ranked using a second round of structure-based virtual screening.
A compound was found that inhibited mammalian TIM in vitro in the micromolar range.
Docking and molecular dynamics (MD) suggested that the inhibitor made hydrogen bond contacts with TIM catalytic residues.
In addition, hydrophobic contacts were made throughout the binding site.
All predicted inhibitor-TIM interactions involved TIM residues that were highly conserved.
The discovered compound may provide a scaffold for elaboration of other inhibitors.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Marsh, Lorraine& Shah, Kaushal. 2014. A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach. International Journal of Medicinal Chemistry،Vol. 2014, no. 2014, pp.1-6.
https://search.emarefa.net/detail/BIM-473950
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Marsh, Lorraine& Shah, Kaushal. A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach. International Journal of Medicinal Chemistry No. 2014 (2014), pp.1-6.
https://search.emarefa.net/detail/BIM-473950
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Marsh, Lorraine& Shah, Kaushal. A Novel Inhibitor of Mammalian Triosephosphate Isomerase Found by an In Silico Approach. International Journal of Medicinal Chemistry. 2014. Vol. 2014, no. 2014, pp.1-6.
https://search.emarefa.net/detail/BIM-473950
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-473950
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر