کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2563582 | 1127544 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Emerging New Technologies in Pharamcogenomics: Rapid SNP detection, molecular dynamic simulation, and QSAR analysis methods to validate clinically important genetic variants of human ABC Transporter ABCB1 (P-gp/MDR1)
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کلمات کلیدی
P-gpMDRABCABC transporter - ABC حمل کنندهP-glycoprotein - P-گلیکوپروتئینQSAR - بزرگسال QSAR analysis - تجزیه و تحلیل QSARQuantitative structure-activity relationship - رابطه ساختاری و فعالیت کمیBBB - سد خونی مغزیblood brain barrier - سد خونی مغزیMD simulation - شبیه سازی MDMolecular dynamic simulation - شبیه سازی پویایی مولکولیPharmacogenomics - فارماکوژنومیکMultidrug resistance - مقاومت چند داروییPersonalized medicine - پزشکی شخصیSingle nucleotide polymorphisms (SNP) - پلیمورفیسم تک نوکلئوتید (SNP)Single nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتیدATP-binding cassette - کیت اتصال به ATP
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
Pharmacogenomics, the study of the influence of genetic factors on drug action, is increasingly important for predicting pharmacokinetics profiles and/or adverse reactions to drugs. Drug transporters as well as drug-metabolism play pivotal roles in determining the pharmacokinetic profiles of drugs and, by extension, their overall pharmacological effects. There are an increasing number of reports addressing genetic polymorphisms of drug transporters. A key requirement for the development of individualized medicine or personalized therapy is the ability to rapidly and conveniently test patients for genetic polymorphisms and/or mutations. We have recently developed a rapid and cost-effective method for single nucleotide polymorphism (SNP) detection, named Smart Amplification Process 2 (SmartAmp2), which enables us to detect genetic polymorphisms or mutations in 30 to 45Â min under isothermal conditions without DNA isolation and PCR amplification. Furthermore, high-speed functional screening, quantitative structure-activity relationship (QSAR) analysis, and molecular dynamic (MD) simulation methods have been developed to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function and substrate specificity. These methods would provide powerful and practical tools for screening synthetic and natural compounds, and the deduced data can be applied to the molecular design of new drugs. This review addresses such new methods for validating genetic polymorphisms of human ABC transporter ABCB1 (P-gp/MDR1) which is critically involved in the pharmacokinetics of drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 126, Issue 1, April 2010, Pages 69-81
Journal: Pharmacology & Therapeutics - Volume 126, Issue 1, April 2010, Pages 69-81
نویسندگان
Toshihisa Ishikawa, Aki Sakurai, Hiroyuki Hirano, Alexander Lezhava, Minoru Sakurai, Yoshihide Hayashizaki,