کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2079814 1401249 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Secondary pharmacology: screening and interpretation of off-target activities – focus on translation
ترجمه فارسی عنوان
فارماکولوژی ثانویه: غربالگری و تفسیر فعالیتهای غیر هدفمند تمرکز بر ترجمه
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
چکیده انگلیسی


• Secondary pharmacology has become an essential element of drug discovery, accepted by the pharmaceutical industry and health authorities.
• Reverse translation defines adverse drug reaction–target associations and generates profiling panels to detect hazards associated with off-targets.
• In vitro experimental approaches allow the use of human targets at early drug discovery.
• In silico tools enable smart chemical design and have become an essential part of off-target mitigation.
• Data linked to preclinical PK observations make it possible to predict clinical outcome and reduce the need for in vivo assessment.

Secondary pharmacology is an essential component of drug discovery and is used extensively in the pharmaceutical industry for achieving optimal specificity of new drugs via early hazard identification and off-target mitigation. The importance of this discipline has been achieved by increasing its translational value, based on the recognition of biological target–drug molecule–adverse drug reaction (ADR) associations and integration of secondary pharmacology data with pharmacokinetic parameters. Information obtained from clinical ADRs, from recognition of specific phenotypes of animal models and from hereditary diseases provides increasing regulatory confidence in the target-based approach to ADR prediction and mitigation. Here, we review the progress of secondary pharmacology during the past decade and highlight and demonstrate its applications and impact in drug discovery.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Discovery Today - Volume 21, Issue 8, August 2016, Pages 1232–1242
نویسندگان
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