کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8514912 | 1556512 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modeling Organic Anion-Transporting Polypeptide 1B1 Inhibition to Elucidate Interaction Risks in Early Drug Design
ترجمه فارسی عنوان
مهار القاء پلی اتیلید آنیون حمل و نقل آلی به منظور تشخیص خطرات تعامل در طراحی اولیه دارو
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کلمات کلیدی
PLSIC50DDIOATPPCA - PCAPrincipal component analysis - تحلیل مولفههای اصلی یا PCADrug interactions - تداخل داروییdrug-drug interaction - تعامل دارو و داروOrganic anion-transporting polypeptide transporters - حمل و نقل پلی پپتید های آنیونی ارگانیزمtwo dimensional - دو بعدیhuman embryonic kidney cells - سلول های کلیوی جنینی انسانHEK cells - سلولهای HEKthree dimensional - سه بعدیcoefficient of determination - ضریب تعیینMolecular modeling - مدل سازی مولکولیorganic anion-transporting polypeptide - پلی اتیلن حمل و نقل آنیونی آلی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
The importance of transporter proteins for the disposition of drugs has become increasingly apparent during the past decade. A noted drug-drug interaction risk is the inhibition of organic anion-transporting polypeptides (OATPs), key transporters for the liver uptake of the widely used statins. We show here the development of a ligand-based in silico model for interaction with OATP1B1, an important representative of the OATP family. The model is based on a structural overlay of 6 known OATP1B1 inhibitors. A data set of about 150 compounds with published OATP1B1 inhibition data was compared to the resulting “transportophor,” and a similarity threshold was defined to distinguish between active and inactive molecules. In addition, using a statistical model based on physicochemical properties of the compounds as prefilter was found to enhance the overall predictivity of the model (final accuracy 0.73, specificity 074, and sensitivity 0.71, based on 126 compounds). The combined model was validated using an in-house data set (accuracy, specificity, and sensitivity were 0.63, 0.59, and 0.78, respectively; 62 compounds). The model gives also a structural overlay to the most similar template enabling visualization of where a change in a given structure might reduce the interaction with the transporter.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 10, October 2016, Pages 3214-3220
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 10, October 2016, Pages 3214-3220
نویسندگان
Ismael Zamora, Susanne Winiwarter,